Biomedical subjects

G A Lincoln

Publications and source records attributed to G A Lincoln.

At least 19 recordsLinked to original sources

PubMed1992

Administration of melatonin into the mediobasal hypothalamus as a continuous or intermittent signal affects the secretion of follicle stimulating hormone and prolactin in the ram.

The biological effects of administering melatonin into the mediobasal hypothalamus (MBH) was documented in adult Soay rams using two delivery systems: (1) microimplants in the MBH delivering melatonin continuously and (2) microdialysis probes in the MBH delivering melatonin intermittently as a daily timed infusion. The experimental protocol was to precondition rams to long days (LD 16:8) for 10 to 12 weeks, and then introduce the exogenous source of melatonin by implantation or infusion. Sixteen rams were divided equally into four treatment groups: (a) microimplants in the MBH, (b) microdialysis probes in the MBH, (c) empty microimplants in the MBH to act as sham-operated controls, and (d) no surgery to act as unoperated controls. The microimplants consisted of 22-gauge stainless steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain for 14 weeks. These implants had previously been shown to release melatonin at a relatively constant rate when incubated in buffered saline at 37 degrees C (3.42 +/- 0.42 micrograms/24 hr, mean +/- SEM, 1-10 weeks) and to produce a localised concentration of melatonin when implanted in the brain (localised to within 1 mm of the center of the implant). The microdialysis probes were also 22-gauge cannulae with a 3 mm membrane (Biotech). They were placed bilaterally into the MBH, connected to two portable syringe drivers secured to a backpack. Melatonin was infused daily for 10 hr (estimated delivery: 0.5 microgram/hr) starting in the mid-light phase to produce a long-duration intermittent melatonin signal. Technical problems limited the period of infusions to 8-10 weeks with minor interruptions. Animals from all groups were maintained on long days, and the observations extended for a period of 28 weeks. The melatonin implants placed in the MBH induced a premature increase in the blood concentrations of FSH and growth of the testes. This treatment also induced a marked decrease in the plasma concentrations of prolactin and the earlier development of the long winter pelage. These changes were reversed after the end of treatment with a decline in the plasma concentrations of FSH and regression of the testes, and an increase in the concentrations of prolactin and moult of the winter pelage. Daily infusions of melatonin from the microdialysis probes in the MBH produced qualitatively similar, but less marked responses. The overall results illustrate that the administration of melatonin into the MBH, either continuously or intermittently, to extend the duration of the daily melatonin signal, induces multiple short-day responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area in rams.

The reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus (MBH) and preoptic area (POA) were monitored in Soay rams. Groups of animals were initially conditioned to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal reproductive cycle. All experiments were then initiated at 10 weeks under long days when the animals were sexually inactive. In experiment 1, rams were exposed to short days for 14 weeks or maintained on long days to illustrate the photoperiodically induced re-activation and regression of the reproductive axis. In experiments 2-4, rams received micro-implants of melatonin in the MBH or POA, or received control treatments (sham-operated or no surgery) for 12-14 weeks while maintained on long days (total of 12 animals/treatment). The melatonin implants consisted of 22-gauge stainless-steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain. Incubation of the implants in Tricine-buffered saline (pH 8.0) at 37 degrees C showed that the release rate of melatonin was relatively constant after an initial peak in week 1 (means +/- S.E.M.: 3.42 +/- 0.43 micrograms/24 h). Rams with melatonin implants placed in the MBH, but not in the POA, showed a consistently earlier re-activation of the reproductive axis compared with the control animals in all three experiments (12/12 for MBH vs 2/12 for POA). The mean time to maximum testicular diameter was 12.2 +/- 0.9, 21.6 +/- 1.8 and 22.3 +/- 1.2 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P less than 0.01; analysis of variance). The premature growth of the testes in the MBH group was associated with an earlier increase in the blood plasma concentrations of FSH and testosterone, and the appearance of the sexual skin coloration. Removal of the implants resulted in a decline in all reproductive parameters. The melatonin treatments did not cause a detectable increase in the peripheral concentrations of melatonin, or affect the diurnal rhythm in melatonin which reflected the long-day photoperiod. When implants containing 125I-labelled melatonin were introduced into the brain the associated radioactivity was localized to within 1 mm of the implants. The overall results demonstrate that the constant administration of melatonin into the MBH blocks the effect of the endogenous long-day melatonin signal and induces gonadal redevelopment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area on the secretion of prolactin and beta-endorphin in rams.

In a previous study, we showed that the local administration of melatonin in the mediobasal hypothalamus (MBH), but not the preoptic area (POA), caused a premature increase in the secretion of FSH and growth of the testes in sexually inactive Soay rams exposed to long days. To extend these observations, we have now measured blood concentrations of prolactin and beta-endorphin and the associated peripheral responses in the same animals, to establish whether the treatments produced multiple endocrine changes such as those which occur following exposure to short days. Groups of rams were initially exposed to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal cycles in the secretion of the pituitary hormones. The treatments were started at 10 weeks under long days, when the animals had a physiology characteristic of the early summer with high blood plasma concentrations of prolactin (associated with growth of the summer pelage), and low concentrations of beta-endorphin (associated with low body weight). The animals were assigned at random to the following treatments: (i) micro-implants of melatonin in the MBH, (ii) microimplants of melatonin in the POA, (iii) empty implants in the MBH or POA to act as operated controls, and (iv) no surgery to act as unoperated controls (n = 12 rams/treatment). The micro-implants consisted of 22-gauge stainless-steel needles with melatonin fused inside the tip. The implants were inserted bilaterally in the brain, and left in place for 12-14 weeks. The observations continued for a total of 28 weeks while the animals remained under long days. The administration of melatonin in the MBH induced a rapid decreased in plasma concentrations of prolactin while in the POA it induced a less marked but significant effect. The mean times to minimum concentrations of prolactin were 7.4 +/- 0.4, 17.3 +/- 2.8 and 26.0 +/- 0.3 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P < 0.001, POA vs control P < 0.01). In the MBH group, the concentrations of prolactin subsequently increased to a maximum 6 weeks after the end of melatonin treatment. The changes in prolactin were accompanied by changes in growth and moulting of the pelage; only animals in the MBH group showed a conspicuous moult associated with the change from low to high prolactin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Phase shifts in the circadian rhythm in plasma concentrations of melatonin in rams induced by a 1-hour light pulse.

The effect of a 1-hr light pulse, given at night, on the timing of the circadian rhythm in the plasma concentration of melatonin was examined in Soay rams to investigate the mechanisms involved in determining the duration of the nocturnal peak in melatonin secretion. Animals (n = 8) were housed under short days (LD 8:16) or long days (LD 16:8) and received a light pulse at various times of night. They were released into constant dim red light (DD) on day 1. Blood samples were collected hourly for 30 hr from 1000 hr on day 3, and the plasma concentration of melatonin was determined by radioimmunoassay to assess the timing of the melatonin peak. Control animals (n = 8) were maintained under the same conditions but received no light pulse. Under short days, a light pulse given early in the night caused a phase delay in the melatonin peak, and a light pulse given in the late night caused a phase advance. The mean duration of the melatonin peak was slightly reduced following a light pulse in the early or late night, and slightly increased following a pulse given near the middle of the night. Under long days, both light-pulse treatments given at night caused a phase delay in the melatonin peak, but there was no significant change in duration of the melatonin peak. The duration of the melatonin peak at day 3 under DD in the control animals was similar for all treatments, regardless of the previous entraining photoperiod (mean duration: 12.6-14.8 hr) and was similar to that under short days (14.6 hr), but was significantly longer than that under long days (8.2 hr). Information on the phase response curve in the Soay ram and on the period of the circadian oscillator governing the melatonin rhythm (c 23.0 hr under DD) predicts a close phase relationship between the end of the light phase and the onset of the melatonin peak as observed under normal 24-hr LD cycles. The current results also indicate that light acts to entrain the circadian rhythm influencing the onset and offset of melatonin secretion, and thus dictates the duration of the melatonin peak.

Animals↗

PubMed1990

Seasonal cycles in the blood plasma concentration of FSH, inhibin and testosterone, and testicular size in rams of wild, feral and domesticated breeds of sheep.

Seasonal cycles in testicular activity in rams were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland and Merino) living outdoors near Edinburgh (56 degrees N). The changes in the blood plasma concentrations of FSH, inhibin and testosterone, and the diameter of the testis were measured every half calendar month from 1 to 3 years of age. There were significant differences between breeds in the magnitude and timing of the seasonal reproductive cycle. In the mouflon rams, the seasonal changes were very pronounced with a 6-15-fold increase in the plasma concentrations of FSH, inhibin and testosterone from summer to autumn, and a late peak in testicular diameter in October. In the Soay rams and most of the domesticated breeds, the seasonal increase in the reproductive hormones occurred 1-2 months earlier with the peak in testicular size in September or October. In the two southern breeds (Portland and Merino), the early onset of testicular activity was more extreme with the seasonal maximum in August. In cross-bred rams, produced by mating Soay ewes (highly seasonal breed) with Portland or Merino rams (less seasonal breeds), there was a seasonal reproductive cycle that was intermediate compared to that of the parents. A comparison between all 11 breeds showed a significant correlation between the timing of the seasonal cycle in plasma FSH concentration and testicular diameter (time of peak FSH vs testis, r = 0.95). The overall results in the rams are consistent with a primary role of FSH in dictating the seasonal cycle in testicular size and the secretion of inhibin. The earlier seasonal onset in the testicular cycle in the southern breeds of domesticated sheep, and the differences from the wild type, are taken to represent the effects of genetic selection for a longer mating season.

Animals↗

PubMed1990

Correlation with changes in horns and pelage, but not reproduction, of seasonal cycles in the secretion of prolactin in rams of wild, feral and domesticated breeds of sheep.

Seasonal cycles were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland, Merino, Soay x Portland and Soay x Merino) living outdoors near Edinburgh (56 degrees N). Changes in the blood plasma concentrations of prolactin and FSH, and growth of the horns and pelage were measured every half calendar month from 1 to 3 years of age. In all breeds there was a clearly defined seasonal cycle in the plasma concentration of prolactin with an 18-66-fold increase in mean values from the nadir in November and December to the peak in May and June. The seasonal increase in prolactin was closely correlated with the seasonal increase in the growth of the horns, both within and between breeds (e.g. time of peak prolactin vs horn growth for 11 breeds, R = 0.62, P less than 0.05). In the mouflon, Soay and some of the domesticated breeds of sheep (Wiltshire, Herdwick and Shetland), the seasonal increase in prolactin was also temporally correlated with the resurgence of growth of the pelage in spring and a conspicuous moult. In the other breeds developed to produce fine wool (e.g. Norfolk, Portland and Merino), there was no clear seasonal change in the pelage and growth continued throughout the year. Comparison between breeds indicated that continuous growth of the pelage was associated with higher plasma prolactin concentrations in winter. The times of the seasonal changes in plasma concentrations of prolactin were not significantly correlated with the corresponding changes in the plasma concentrations of FSH. The overall results are consistent with a role for prolactin related to the growth of the horns and pelage rather than the seasonal cycle in reproduction. The differences between the wild-type and the domesticated breeds in the pelage represent the effect of selective breeding to produce a long fine fleece which has involved changes in both the seasonal pattern of prolactin secretion and the growth characteristics of the hair fibres.

Animals↗

PubMed1990

Regulation of the seasonal cycle of beta-endorphin and ACTH secretion into the peripheral blood of rams.

In a group of 12 adult Soay rams living outdoors near Edinburgh there was a conspicuous seasonal cycle in the peripheral plasma concentrations of beta-endorphin, ACTH and cortisol. The concentration of all three hormones increased 5- to 20-fold from winter to summer; the seasonal maximum occurring from May to July for ACTH and cortisol and in August for beta-endorphin. At the peak of the cycle the ratio of beta-endorphin to N-acetyl-beta-endorphin was 22:1. The regulation of the seasonal cycle was investigated in a series of five experiments involving treatments with arginine vasopressin (AVP), corticotrophin-releasing factor (CRF) and the synthetic glucocorticoid, dexamethasone. Injection of AVP i.v. induced a dose-dependent increase in the plasma concentration of beta-endorphin (AVP doses of 0, 0.07, 0.33 and 1.67 micrograms/kg). AVP (0.33 micrograms/kg) and CRF (1.67 micrograms/kg) given alone or in combination (equimolar doses), induced an increase in the plasma concentrations of beta-endorphin and ACTH in spring, summer, autumn and winter, and produced a synergistic response when given together. The responses varied with season and were greatest in summer and autumn at the time of the seasonal increase in endogenous secretion. Dexamethasone injected i.v. at 68.04 micrograms/kg produced a decrease in the plasma concentrations of beta-endorphin and ACTH, and the responses were also greatest in summer and autumn. A similar treatment with dexamethasone blocked the AVP-induced increase in the plasma levels of beta-endorphin, indicating an action of dexamethasone on the pituitary gland. Administration of ACTH (0.33 micrograms/kg; i.v.) to rams pretreated with dexamethasone stimulated an increase in the plasma concentration of cortisol; this response varied with season, being greatest in spring at the time of the peak in the seasonal cycle in cortisol secretion. The administration of beta-endorphin (0.33 micrograms/kg) failed to induce an increase in the plasma levels of cortisol at any season. Analysis of the hormone profiles in the control rams based on blood samples collected every 10 min for 8 h revealed pulsatile variations in the plasma concentration of ACTH; some of the spontaneous ACTH peaks were correlated with beta-endorphin peaks. From these results in the Soay ram, we conclude that beta-endorphin and ACTH are co-secreted from the pituitary gland following stimulation by AVP and CRF, and that adrenal glucocorticoids stimulated by ACTH can act in a negative feedback role at the level of the pituitary gland to inhibit the release of both beta-endorphin and ACTH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1990

Regulation of the photoperiod-induced cycle in the peripheral blood concentrations of beta-endorphin and prolactin in the ram: role of dopamine and endogenous opioids.

In a group of adult Soay rams housed indoors under an artificial light cycle of alternating 16-week periods of long and short days, there was a conspicuous long-term cycle in the peripheral plasma concentrations of beta-endorphin and prolactin. The levels of beta-endorphin were highest under short days and lowest under long days (15-fold change), and inversely related to the changes in the plasma levels of prolactin (120-fold change). The role of dopamine in the control of beta-endorphin and prolactin was investigated in a series of experiments, conducted under both long and short days, in which rams were treated with dopamine receptor agonists (dopamine and bromocriptine) and antagonists (pimozide and sulpiride). Naloxone (opioid antagonist) was also administered to assess the additional involvement of endogenous opioids. Dopamine injected i.v. (6.6 mg/kg every 10 min) did not significantly affect the mean plasma concentrations of beta-endorphin and prolactin under either long or short days. Pimozide (0.08 mg/kg i.m. every 2 h) caused a large increase in the mean plasma concentrations of beta-endorphin and prolactin under long days but not short days. Naloxone (1.6 mg/kg, i.v.), administered alone or in combination with dopamine or pimozide, had no effect on the mean plasma concentrations of beta-endorphin and prolactin, except under short days when, combined with pimozide, it induced an increase in the plasma concentrations of the two polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Long-term reproductive cycles in rams after pinealectomy or superior cervical ganglionectomy.

Long-term cycles in diameter of the testes, colouration of the sexual skin and plasma concentrations of testosterone, FSH and prolactin were monitored in groups of pinealectomized (PINX), superior cervical ganglionectomized (SCGX), and control Soay rams living near Edinburgh (56 degrees N). In Exp. 1, PINX, SCGX and control rams were kept outside for 4 years, and well defined seasonal cycles in each of the reproductive parameters were evident in all 3 groups (e.g. testosterone cycle length assessed by sine-wave analysis: 12.08 +/- 0.17, 12.39 +/- 0.14 and 12.15 +/- 0.10 months for PINX, SCGX and control rams respectively). Qualitative differences, however, were apparent between the groups in the timing and amplitude of the reproductive cycle. The seasonal peak in reproductive function occurred from July to September in the PINX and SCGX rams, some 2 months earlier in the year than in controls, while the amplitude of the cycle was less marked in the PINX and SCGX rams. There were no significant differences between the experimental groups in the seasonal cycle in the plasma concentrations of prolactin. In Exp. 2, SCGX and control rams were kept indoors under an artificial environment with a 32-week light cycle and constant nutrition for 4 years. Compared to the controls, in which the reproductive changes were synchronized to the driving light cycle, the SCGX rams showed poorly defined reproductive cycles of lower amplitude and longer period (e.g. testosterone cycle length: 57.8 +/- 6.1 and 32.1 +/- 0.2 weeks for SCGX and control rams, respectively). There was evidence of a cycle in some of the reproductive parameters in the SCGX rams with a period close to 32 weeks during the second half of the study (e.g. testosterone cycle 32.4 +/- 0.8 weeks), which was taken to indicate social induction from the neighbouring control rams. In two further short-term experiments, SCGX rams showed a decline in testicular activity in response to receiving a restricted diet (60% of controls) and an increase in testosterone secretion in response to exposure to oestrous ewes. The overall results illustrate that PINX and SCGX rams can generate long-term synchronized cycles in pituitary and testicular activity. The animals are apparently unable to respond to changes in daylength due to the loss of the functional pineal gland but they remain competent to respond to other environmental cues such as changes in nutrition, temperature and social factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Test of ML23 as an antagonist to the effects of melatonin in the ram.

In Exp. 1, four groups of 8 yearling Soay rams were housed under long days (16L:8D) to induce reproductive quiescence and were treated daily for 12 weeks with: (I) vehicle (2 or 4 ml 50% ethanol/water), (II) ML23 (2 mg), (III) melatonin (2 mg) and (IV) melatonin and ML23 (2 mg of each). All treatments were given orally in the mid-light phase. In the rams receiving melatonin (Group III) there was an earlier increase in the plasma concentrations of FSH and testosterone and regrowth of the testes compared to the controls (time to maximum testicular diameter: 10.0 +/- 0.5 and 15.3 +/- 1.2 weeks). These differences were reversed after the end of the 12-week treatments when rapid testicular regression occurred in melatonin-treated rams but not in the controls. In the group receiving ML23 and melatonin (Group IV), there was early reactivation and regression of the reproductive axis as in the melatonin group (testis max. 9.9 +/- 0.7 and 10.0 +/- 0.5 weeks) while in the group receiving ML23 alone (Group II) there was a slower redevelopment and regression as in the controls (testis max. 15.7 +/- 1.1 and 15.3 +/- 1.2 weeks). The comparison between the 4 groups in the changes in the blood concentrations of prolactin, voluntary food intake and total body weight also indicated that the treatment with ML23 failed to modify the effect of melatonin (combined treatment vs melatonin) or the effect of the long day photoperiod (ML23 vs vehicle).(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine↗

PubMed1989

Inhibin concentrations in the peripheral blood of rams during a cycle in testicular activity induced by changes in photoperiod or treatment with melatonin.

Changes in the concentration of inhibin, FSH, LH and testosterone were measured in the peripheral blood of adult Soay rams during a reproductive cycle induced by exposure to an artificial lighting regimen (long days with a 16-week period of short days) or treatment with melatonin (long days with a 12-week period when melatonin was administered daily in mid-light phase to simulate the effect of short days). In both experimental situations, changes in the plasma concentrations of inhibin occurred in parallel with the cycle in the diameter of the testes with a four- to fivefold increase in the inhibin concentrations from the nadir to the peak of the testicular cycle. Increases in the plasma concentrations of FSH, LH and testosterone also occurred in association with the reactivation of the reproductive axis. The weekly changes in the plasma concentrations of inhibin were positively correlated with the changes in plasma FSH values during the developing and regressing stages of the testicular cycle but negatively correlated during the active stage. In a group of castrated rams exposed to the same lighting regimen, the plasma concentrations of inhibin were always below the detection limit of the radioimmunoassay. The testosterone values were also very low in the castrates while the plasma concentrations of FSH and LH were 10-50 fold higher than normal and varied in relation to the light cycle. The results show for the first time that inhibin is secreted into the peripheral blood in the ram exclusively from the testes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Endogenous opioids and the control of LH secretion during the reproductive cycle in the ram induced by treatment with melatonin.

To investigate the role of endogenous opioid peptides (EOP) in the inhibitory control of LH secretion in the ram, the acute effects of naloxone (opioid antagonist) on episodic LH secretion were measured in rams at different stages of a reproductive cycle induced by treatment with melatonin. Groups of SCGx rams (functionally pinealectomized) and pineal intact rams were housed under long days (16 h light: 8 h darkness) and treated with alternating 16 week periods with exogenous melatonin (continuous melatonin from silastic implant) and 16 week periods with no exogenous melatonin for 3 or 4 consecutive cycles. The LH response to naloxone (1.6 mg/kg i.v.) was measured at 2-4 week intervals on 9 occasions during one of the treatment cycles. The periodic treatment with melatonin resulted in a clearly defined cycle in the plasma concentrations of LH, FSH, testosterone and prolactin, and associated changes in size of the testes, intensity of the sexual skin flush and moulting of the pelage; maximum size of the testes occurred 8-16 weeks after the start of each melatonin treatment. Naloxone induced an increase in plasma LH concentrations at all times but the response varied in relation to the stage of the melatonin-induced reproductive cycle. During testicular recrudescence, naloxone induced large increases in mean LH concentration (low frequency, high amplitude LH pulses), at the peak of the reproductive cycle naloxone induced smaller increases in plasma LH (high frequency, low amplitude pulses) and during testicular regression naloxone induced only minor increments in plasma LH. The results are consistent with the role of EOP in the inhibitory control of LH secretion with this system most active during the sexually active phase of the reproductive cycle.

Animals↗

PubMed1988

Effects of constant darkness and constant light on circadian organization and reproductive responses in the ram.

The relationship between circadian rhythms in the blood plasma concentrations of melatonin and rhythms in locomotor activity was studied in adult male sheep (Soay rams) exposed to 16-week periods of short days (8 hr of light and 16 hr of darkness; LD 8:16) or long days (LD 16:8) followed by 16-week periods of constant darkness (dim red light; DD) or constant light (LL). Under both LD 8:16 and LD 16:8, there was a clearly defined 24-hr rhythm in plasma concentrations of melatonin, with high levels throughout the dark phase. Periodogram analysis revealed a 24-hr rhythm in locomotor activity under LD 8:16 and LD 16:8. The main bouts of activity occurred during the light phase. A change from LD 8:16 to LD 16:8 resulted in a decrease in the duration of elevated melatonin secretion (melatonin peak) and an increase in the duration of activity corresponding to the changes in the ratio of light to darkness. In all rams, a significant circadian rhythm of activity persisted over the first 2 weeks following transfer from an entraining photoperiod to DD, with a mean period of 23.77 hr. However, the activity rhythms subsequently became disorganized, as did the 24-hr melatonin rhythms. The introduction of a 1-hr light pulse every 24 hr (LD 1:23) for 2 weeks after 8 weeks under DD reinduced a rhythm in both melatonin secretion and activity: the end of the 1-hr light period acted as the dusk signal, producing a normal temporal association of the two rhythms. Under LL, the 24-hr melatonin rhythms were disrupted, though several rams still showed periods of elevated melatonin secretion. Significant activity rhythms were either absent or a weak component occurred with a period of 24 hr. The introduction of a 1-hr dark period every 24 hr for 2 weeks after 8 weeks under LL (LD 23:1) failed to induce or entrain rhythms in either of the parameters. The occurrence of 24-hr activity rhythm in some rams under LL may indicate nonphotoperiodic entrainment signals in our experimental facility. Reproductive responses to the changes in photoperiod were also monitored. After pretreatment with LD 8:16, the rams were sexually active; exposure to LD 16:8, DD, or LL resulted in a decline in all measures of reproductive function. The decline was slower under DD than LD 16:8 or LL.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

LHRH and beta-endorphin in the hypothalamus of the ram in relation to photoperiod and reproductive activity.

The regional distribution and relative concentrations of LHRH and beta-endorphin immunoreactivity in the hypothalamus were compared in sexually active and sexually inactive Soay rams. LHRH was localized principally in the medial basal hypothalamus and median eminence with lower concentrations in the anterior hypothalamus and preoptic area. beta-endorphin immunoreactivity was also found in highest concentrations in these regions but was more widely distributed into the rostral, dorsal and lateral parts of the hypothalamus. LHRH content in the medial basal hypothalamus was significantly lower in the sexually active rams compared to inactive rams while there was no difference in beta-endorphin immunoreactivity content between the two groups. Gel filtration chromatography of hypothalamic extracts revealed that the beta-endorphin immunoreactivity was due to both beta-lipotropin and beta-endorphin; the ratio of beta-endorphin: beta-lipotropin tended to be less in the sexually active rams than in the sexually inactive rams. The results are consistent with the hypothesis that beta-endorphin is a physiologically important endogenous opioid involved in the modulation of LHRH secretion.

Animals↗

PubMed1987

Beta-endorphin secretion in rams related to season and photoperiod.

A newly established RIA was used to measure changes in the concentration of beta-endorphin in peripheral blood and pituitary tissue from adult Soay rams living outside under natural conditions and housed indoors under artificial photoperiods. A pronounced seasonal cycle in plasma beta-endorphin immunoreactivity occurred in the outdoor animals, with low levels in spring and early summer (February-May; less than 200 pg/ml plasma) and maximal levels 10-20 times higher in late summer and autumn (July-October). Seasonal changes in plasma levels of PRL, FSH, and cortisol, testis size, and body weight were also monitored; the seasonal cycle in the levels of immunoreactive beta-endorphin occurred in parallel with the cycle in plasma FSH and body weight. There were no significant seasonal changes in plasma cortisol concentrations. Marked changes in the plasma levels of beta-endorphin were also seen in rams kept under the artificial photoperiod regimen of alternating 12- to 16-week periods of long days (16 h of light and 8 h of darkness; 16L:8D) and short days (8L:16D). Transfer from long days to short days led to a greater than 20-fold increase in the levels of beta-endorphin, reaching a maximum after 4-8 weeks; the reverse switch in photoperiod led to a rapid decrease in the levels. There was no diurnal rhythm in the plasma levels of beta-endorphin based on hourly samples collected for 24 h under long and short days. The total content of immunoreactive beta-endorphin in the pituitary gland was lower in rams under short days than under long days, converse to the pattern in the blood. Sephadex chromatography of the plasma samples revealed that most of the beta-endorphin immunoreactivity coeluted with synthetic beta-endorphin-(1-31), and a small amount of activity eluted with beta-lipotropin. The seasonal and photoperiod-induced changes were largely due to changes in the levels of beta-endorphin. Extracts of pituitary tissue revealed a large proportion of beta-lipotropin to beta-endorphin compared to plasma, with no consistent change in ratio related to the photoperiod. The overall results illustrate that there are pronounced seasonal and photoperiod-induced changes in immunoreactive plasma beta-endorphin levels in the ram. Under artificial photoperiods, long days inhibit and short days stimulate beta-endorphin secretion. Under natural conditions, the development of refractoriness to both the inhibitory effects of long days and the stimulatory effects of short days may explain the timing of the annual cycle of beta-endorphin secretion.

Animals↗

PubMed1987

Compensatory response of the luteinizing-hormone (LH)-releasing hormone (LHRH)/LH pulse generator after administration of a potent LHRH antagonist in the ram.

It is established that the blockade of the pituitary LHRH receptor by an LHRH antagonist will suppress pituitary LH secretion and reduce serum concentrations of gonadal steroids. Little is known, however, about the activity of the LHRH/LH pulse generator during this inhibitory period or during the recovery phase. To investigate this, a potent LHRH antagonist [N-Ac-D-pCl-Phe1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6, D-Ala10 LHRH was injected iv into sexually active rams and the changes in the blood plasma concentrations of LH, FSH, testosterone, and PRL were measured in samples collected every 15 min for 24-48 h. The treatment induced an immediate blockade of pulsatile LH secretion and a parallel decline in blood levels of testosterone. Plasma levels of FSH were not suppressed by treatment with the LHRH antagonist and there was no consistent effect on plasma levels of PRL. The duration of the inhibition of LH was dose dependent lasting 4.3 +/- 0.4 h, 18.0 +/- 1.0 h, and 31.8 +/- 1.3 h for the low (6 micrograms/kg), medium (36 micrograms/kg), and high (365 micrograms/kg) doses of LHRH antagonist, respectively. During the recovery period there was an approximate 2-fold increase in the frequency of LH pulses. These results suggest a compensatory response to the decline in the negative feedback effect of testosterone secretion. Even the lowest dose of antagonist elicited a decrease in the level of testosterone and an increase in LH pulse frequency. At this dose, the decline in testosterone was very transitory indicating an acute sensitivity of the hypothalamus to changes in the negative feedback signal. These results suggest that the suppression of LH and testosterone secretion in the ram by LHRH antagonist is associated with a compensatory increase in the activity of the LHRH pulse generator.

Animals↗

PubMed1987

Long-term stimulatory effects of a continuous infusion of LHRH agonist on testicular function in male red deer (Cervus elaphus).

Red deer stags were infused continuously with the LHRH agonist buserelin at 180-270 micrograms/day (1.2-1.8 micrograms/kg/day) for 72 days starting in late winter with the aim of suppressing reproductive function and inducing premature casting of the antlers. Contrary to expectation, the treatment resulted in a long-term stimulation of testicular activity lasting at least 2 months; the increases in plasma concentrations of testosterone were associated with an increase in aggressive behaviour and the development of rutting odour in the urine. The stags cast their antlers at the normal time in spring after the end of the treatments. The results indicate that the pituitary gonadotroph cells in the stag can continue to secrete LH in response to chronic exposure to an LHRH agonist and do not become rapidly desensitized. The effect of the agonist is therefore to cause significant stimulation of testicular activity which is a conspicuous response in the non-breeding season when the stags are already in a hypogonadal state.

Animals↗

PubMed1987

Endogenous opioid control of pulsatile LH secretion in rams: modulation by photoperiod and gonadal steroids.

The role of endogenous opioid peptides in the inhibitory control of pulsatile LH secretion was studied in adult Soay rams at different stages of the seasonal reproductive cycle, entrained by an artificial lighting regimen of alternating 16-week periods of long and short days. The LH responses to the acute administration of naloxone (opioid antagonist) and morphine (opioid agonist) were measured in intact rams (n = 7), testosterone-implanted castrated rams (n = 8) and castrated rams (n = 8) to assess the interaction between photoperiod and gonadal steroids in the opioid control of LH secretion. In the intact and testosterone-implanted castrated rams, naloxone (1.7 mg/kg i.v.) increased and morphine (1.0 mg/kg i.v.) decreased mean LH concentrations and LH pulse frequency during the sexually active phase under short days, but these effects were reduced or absent during the inactive phase under long days. The changes in the LH responses occurred in close parallel with the photoinduced changes in endogenous LH secretion. In the castrated rams receiving no supplementary testosterone, plasma LH concentrations were permanently raised and there were only minor changes related to the photoperiod. Naloxone (1.7 mg/kg) induced transient increases in LH secretion at all stages, and morphine (1.0 mg/kg) failed to suppress LH levels under both short and long days. LHRH stimulation tests revealed that there were changes in LH release related to the induced reproductive cycle in the intact and testosterone-implanted rams but not in the castrated rams; these changes in the responsiveness of the pituitary gonadotrophs to LHRH could not account for the changes in the LH response to the opiate drugs. These results illustrate that an endogenous opioid mechanism is involved in the tonic inhibition of LH secretion acting to regulate the pulsatile release of LHRH from the hypothalamus. This system can be shown to be functional in a steroid-dependent manner in the sexually active phase of the seasonal cycle, but not in the inactive phase of the cycle when non-opioidergic mechanisms are presumed to predominate in the inhibition of LH secretion.

Animals↗