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Biomedical subjects

F J Cunningham

Publications and source records attributed to F J Cunningham.

At least 37 records · Page 2Linked to original sources

Hypothalamic contents of LHRH and catecholamines during the ovulatory cycle of the hen (Gallus domesticus).

Concentrations of LHRH, dopamine, noradrenaline and adrenaline in the anterior hypothalamus-preoptic region (AH-POR) and posterior hypothalamus-median eminence (PH-me) were determined in hens killed at different times in relation to the first ovulation of a sequence. The occurrence of a preovulatory rise in plasma LH concentration 4-6 h before the expected time of ovulation was confirmed. This rise in plasma LH was accompanied by a significant (P less than 0.01) 50% reduction in the LHRH content of the AH-POR and PH-me while the subsequent fall in plasma LH was accompanied by a restoration of the LHRH content of both regions to their former levels. Although no significant fluctuations in the hypothalamic content of either dopamine, noradrenaline or adrenaline were detected during the ovulatory cycle, significant correlations between LHRH content and catecholamine content were observed in the AH-POR (P less than 0.05) and PH-me (P less than 0.01). Thus mean levels of each amine followed the same temporal pattern as LHRH content with minimum values being observed shortly before the peak of the preovulatory surge of LH. These findings support the conclusion that an enhanced secretion of LHRH from the median eminence, possibly associated with an increased activity of catecholaminergic neurones, is a prerequisite for the preovulatory release of LH in the hen.

Animals↗

Developmental changes in the diurnal rhythm of secretion of corticosterone and LH in the domestic hen.

When diurnal changes in the plasma concentrations of corticosterone and LH were compared at various times during sexual development a diurnal rhythm in the secretion of corticosterone was most pronounced at 4.5 weeks of age in hens maintained on a schedule of 8 h light: 16 h darkness (8L: 16D) and at 8.5 weeks of age in hens maintained on 16L: 8D. At these ages the phase-angle of the rhythm in relation to the onset of darkness was 3 h earlier than had been observed in previous studies of the adult hen. The characteristics of the corticosterone rhythm changed during sexual development and diurnal changes were no longer evident in hens at 17 weeks of age at a time when prepubertal plasma concentrations of LH were maximal. However, there was a tendency for plasma concentrations of corticosterone to fluctuate diurnally in hens studied at less than 10 days before the onset of lay although not to the same extent as has previously been observed in the adult hen. This period of development was associated with a pronounced increase in the plasma concentration of progesterone. An increase in the plasma concentration of LH at the onset of darkness was observed at all ages in hens maintained on either photoschedule . In hens of 4.5-15 weeks of age maintained on 16L: 8D or 8L: 16D this increase in the plasma concentration of LH was sustained during the first 5 or 8-11 h of darkness respectively but at 17 weeks of age only a transient increase in LH was seen at the onset of darkness. Plasma concentrations of LH in samples of plasma taken at intervals of between 3 days and 2 weeks throughout sexual development were, until 18-19 weeks, consistently higher in hens maintained on a photoschedule of 16L: 8D than on 8L: 16D.

Animals↗

Effects of infusion of thyrotrophin releasing hormone and dopamine either alone or in combination on plasma prolactin concentrations in the anoestrous ewe.

Plasma concentrations of prolactin in anoestrous ewes were respectively lowered or raised by the separate infusion of dopamine or thyrotrophin releasing hormone (TRH). Combined treatment with dopamine and TRH lowered the concentration of prolactin in plasma but the values increased markedly after the treatment was stopped and reached a level equivalent to that found in ewes treated with TRH alone. The results are interpreted as evidence that both dopamine and TRH play a regulatory role in determining the secretion of prolactin in the ewe.

Anestrus↗

Concentrations of immunoreactive luteinizing hormone releasing hormone in discrete brain regions of the cockerel: effects of castration and testosterone replacement therapy.

The validity of using a radioimmunoassay employing an antiserum raised against synthetic luteinizing hormone releasing hormone (LH-RH) for the quantification of luteinizing hormone releasing factor (LH-RF) in birds was investigated. Extracts of avian hypothalamus yielded displacement curves which were parallel to that of the synthetic LH-RH standard and the immunoreactive potencies of a number of extracts assayed concurrently using two different anti-LH-RH sera were found to be similar. Moreover, after chromatography of cockerel hypothalamic extract on carboxymethyl-cellulose, immunoreactive and biologically active LH-RF were found in the same eluate fractions. Immunoreactive LH-RH was shown to be widely distributed in cockerel hypothalamus with the highest concentrations present in the mediobasal hypothalamus (MBH; 6.55 +/- 1.86 pg/microgram protein, n = 6) and medial preoptic region (POR; 0.95 +/- 0.07 pg/microgram protein, n = 6). The postcastration rise in plasma LH in the cockerel was accompanied by significant (P less than 0.05) increases in the concentration of LH-RH in five hypothalamic areas including the POR; testosterone replacement therapy completely reversed these effects. Although castration raised the mean concentration of LH-RH in four other hypothalamic areas including the MBH, these differences were not significant. However, testosterone replacement therapy depressed LH-RH in all four regions to levels significantly (P less than 0.05) less than those in castrated cockerels. These findings constitute the first direct evidence that the negative feedback action of testosterone on LH secretion in the cockerel is mediated, at least in part, by an action on hypothalamic LH-RF-producing neurones.

Animals↗

An investigation of diurnal and cyclic changes in the secretion of luteinizing hormone in the domestic hen.

The characteristics of the diurnal rhythm in the concentration of LH in plasma of the domestic hen varied according to age and duration of photoperiod. A pronounced increase in LH was observed at the onset of darkness in immature hens whether maintained on schedules of 16 h light: 8 h darkness (16L:8D) or 8L:16D. During weeks 4.5-15 or -17.5 raised concentrations of LH were maintained until 6 and 12 h after the onset of darkness in hens held on 16L:8D and 8L:16D respectively. By 19 weeks of age the diurnal rhythm of LH secretion had changed to resemble more closely that observed in the laying hen. An increase in the concentration of LH in plasma at the onset of darkness was of comparatively short duration and gave way, within 2-3 h, to a steep decline before a further slight increase in LH, which tended to occur at 11-14 h after the onset of darkness. Superimposed on this diurnal rhythm of LH secretion in the laying hen were a one- to threefold increase in the concentration of LH during 8-4 h before ovulation and a much less pronounced increase in LH during 0-8 h after ovulation. The pattern of changes in the concentration of LH in plasma during the ovulatory cycle was not modified by the repeated withdrawal of blood at intervals of 2 h.

Animals↗

Evidence for the involvement of central conversion of testosterone to oestradiol-17 beta in the regulation of luteinizing hormone secretion in the cockerel.

Treatment of intact cockerels with the synthetic antioestrogen tamoxifen caused a significant increase in the plasma concentration of LH. In contrast, passive immunization with an antiserum raised against oestradiol-17 beta did not lead to an increase in plasma LH. A pronounced depressive effect of injections of 0.1 mg testosterone propionate (TP) or 0.1 mg oestradiol benzoate (OB) on plasma concentrations of LH was prevented by tamoxifen. Furthermore, a pronounced rise in the concentration of LH releasing hormone in the posterior hypothalamus after the injection of cockerels with OB was completely inhibited by tamoxifen. Neither 0.1 nor 0.5 mg androstenedione modified the concentration of LH in plasma. A dose of 0.05 mg TP, which failed to depress the concentration of LH in plasma of intact cockerels, caused a marked fall in plasma LH in castrated cockerels. Tamoxifen itself exhibited weak oestrogen agonist activity in castrated cockerels by causing a reduction in the concentration of LH in plasma. However, tamoxifen prevented any further depressive effect on LH resulting from the injection of TP. These findings suggest that testosterone exerts an inhibitory influence on LH secretion at the central neural level, partially at least, by means of the product of its aromatization, oestradiol-17 beta.

Animals↗

Gonadotrophin, total oestrogen and progesterone concentrations in plasma of lactating sows with particular reference to lactational oestrus.

Plasma concentrations of LH, FSH, progesterone and total oestrogens were determined (by radioimmunoassay) throughout late pregnancy and lactation in samples taken by cardiac catheter from 10 Camborough hybrid sows. At 2-3 weeks post partum, 5 were housed individually with their litters (Group I) and 5 grouped with their litters, a boar being introduced 1 day later (Group II). Plasma progesterone fell 1-2 days per partum and oestrogens at parturition, each remaining low in early lactation. Plasma LH was undetectable in most samples in this period, but FSH fell slightly during parturition, showing signs of resurgence from Day 10 post partum. Group I sows remained in lactational anoestrus until weaning. In Group II there was increased plasma LH activity, and all Group II sows displayed oestrus during lactation. Only one farrowed to service at the lactational oestrus; of the remainder, oestrus in one was clearly anovulatory, and in two others was incomplete or atypical judged by plasma progesterone concentrations. The data suggest that whilst oestrus can be induced by appropriate lactation management, poor conception rates to service at this oestrus may be due to the absence or impairment of ovulation.

Animals↗

Effects of metoclopramide and bromocriptine on prolactin secretion in the pregnant ewe.

Metoclopramide and bromocriptine, drugs which are respectively antagonistic and agonistic to dopamine receptor activity, were used to investigate the control of prolactin secretion in the ewe during pregnancy. Normal concentrations of prolactin were found during pregnancy, i.e. values were low and stable during the first 100 days but thereafter increased progressively to reach maximum values at day 140. Treatment with bromocriptine suppressed levels to undetectable values (less than 1.4 micrograms/l plasma) between days 40 and 100 of pregnancy. Later in gestation, however, bromocriptine administered between days 120 and 140 was less effective, indicating that the pituitary gland was less responsive to the same degree of inhibition. Treatment with metoclopramide alone provoked a progressively greater release of prolactin as pregnancy advanced whereas in bromocriptine-treated animals an associated release of prolactin in response to metoclopramide was seen only between days 120 and 140 of pregnancy. These results are interpreted as evidence that the raised concentrations of prolactin characteristic of late pregnancy in the ewe are due to a reduced responsiveness of the pituitary gland to inhibitory stimuli, or to a decreased secretion of endogenous dopamine into the hypophysial portal blood system or to both.

Animals↗

Evidence for the involvement of central catecholaminergic mechanisms in mediating the preovulatory surge of luteinizing hormone in the domestic hen.

The effects of various pharmacological treatments, designed to perturb central catecholaminergic neurotransmission, on the pattern of LH release during the preovulatory period in the domestic hen were studied. Treatment of hens with either L-dihydroxyphenylalanine or diethyldithiocarbamate which raised the concentration of dopamine in the hypothalamus by 42 and 110% respectively, or with apomorphine, attenuated the preovulatory surge of LH. In contrast, treatment with either alpha-methyl-p-tyrosine which produced a 65% decline in the concentration of dopamine in the hypothalamus without affecting the concentrations of noradrenaline or adrenaline or treatment with pimozide did not affect the LH surge. While treatment with propranolol was similarly ineffective, phenoxybenzamine attenuated the LH surge to a marked extent. These observations suggest that the preovulatory surge of LH in the hen is influenced by facilitatory alpha-adrenergic and inhibitory dopaminergic mechanisms. Evidence to corroborate these findings was sought by determining the steady-state concentrations of dopamine, noradrenaline and adrenaline in five discrete diencephalic regions of the hen throughout the ovulatory cycle.

Adrenergic alpha-Agonists↗

Effect of removal of lambs or treatment with bromocriptine on plasma concentrations of prolactin and FSH during the post-partum period in ewes lambing at different times during the breeding season.

Daily determinations of FSH and prolactin in plasma were made for 10-12 weeks after parturition in ewes which lambed either in the middle of (December) or late in (February) the breeding season. Fluctuations in the plasma concentrations of FSH could not be related to the time after parturition or to the occurrence of otherwise of oestrus and ovulation. However, there was evidence of an increased secretion of prolactin post partum but only in those ewes which lambed in February. The lack of an elevated level of prolactin during the post-partum period in the December-lambing ewes was associated with an earlier return to oestrus by these animals. The suppression of prolactin concentrations by treatment with bromocriptine to undetectable values in the December-lambing ewes was not associated with an earlier return to oestrus. The removal of lambs at various times post partum from those ewes which lambed in February was not associated with any marked changes in prolactin secretion. The results suggest that when the plasma concentrations of prolactin are low post partum there is a greater likelihood of an earlier resumption of breeding activity in the ewe.

Animals↗

Effect of TRH on the secretion of prolactin in ewes at various stages of pregnancy and in non-pregnant ewes during the breeding season and seasonal anoestrus.

The concentrations of prolactin in plasma were measured before and after the injection of TRH in pregnant ewes and in non-pregnant ewes during the breeding season and seasonal anoestrus. During the first 80 days of pregnancy basal concentrations or prolactin were low and stable but thereafter increased progressively to reach maximum values at Day 140. During a comparable time of year (December-April) basal concentrations of prolactin in non-pregnant ewes were not significantly different from those found between Days 20 and 120 of pregnancy. At other times of the year basal concentrations of prolactin in non-pregnant ewes were elevated during anoestrus and declined markedly at the onset of the breeding season. In pregnant and non-pregnant ewes the responsiveness of the pituitary gland to stimulation with TRH was significantly correlated with the basal concentration of prolactin in plasma: the raised concentration of prolactin at Day 140 of pregnancy and in July in non-pregnant ewes was associated with the greatest release of prolactin from the pituitary gland. A change in the responsiveness of the pituitary gland may play an important role in the overall control of prolactin secretion in the ewe.

Anestrus↗

Effects of an anti-oestrogen, tamoxifen (ICI 45,474), on luteinizing hormone release and ovulation in the hen.

The role of oestradiol in the regulation of LH release in the hen was studied by use of the anti-oestrogen, tamoxifen (ICI 46,474). Intramuscular injection of laying hens with 2 or 4 mg tamoxifen on 2 successive days delayed or prevented the occurrence of the preovulatory release of LH and ovulation expected on day 3. Ovulation could be restored by i.v. injection of 20 micrograms LH releasing hormone (LH-RH). Tamoxifen at a dose of 1 mg affected neither the timing of the preovulatory release of LH nor ovulation. Treatment with 2 or 4 mg tamoxifen on 2 successive days reduced the effectiveness of an i.m. injection of progesterone to stimulate a release of LH. Injection of 1, 2 or 4 mg tamoxifen on 2 successive days significantly raised basal levels of LH in the blood at 24 h after the last injection. This was associated with an increase in the capacity of the pituitary gland to respond to an injection of synthetic LH-RH by a release of LH. These studies suggest that oestradiol has at least two roles in the regulation of LH release in the hen. First, it maintains a low basal level of LH-RH. Secondly, oestradiol has a facilitative role in the mechanism by which progesterone stimulates the preovulatory release of LH.

Animals↗

Effect of gonadectomy on the concentrations of catecholamines in discrete areas of the diencephalon of the domestic fowl.

Concentrations of dopamine, noradrenaline and adrenaline in discrete areas of the diencephalon in male and female domestic fowl were correlated with changes in the plasma concentrations of LH induced by gonadectomy. Gonadectomized birds of both sexes exhibited raised plasma concentrations of LH and in castrated cockerels the daily administration of testosterone propionate was completely effective in preventing the postcastration rise in LH. Although no significant alterations in the brain concentrations of noradrenaline or adrenaline were observed in cockerels, the concentration of dopamine in the paraventricular nucleus (PVM), dorsomedial thalamic nucleus and mediobasal hypothalamus (MBH) were significantly raised in castrated compared with sham-operated birds by 136, 182 and 52% respectively. In each case the increase was partially suppressed by testosterone replacement therapy. In pullets, ovariectomy resulted in significant increases in the concentrations of dopamine (83%) and noradrenaline (78%) in the MBH and noradrenaline (35%) and adrenaline (34%) in the PVM. These findings suggest that in the fowl at least part of the negative feedback effect of gonadal steroids on LH secretion may be mediated by catecholaminergic mechanisms at the level of the hypothalamus.

Animals↗

Effect of photoperiod on the concentrations of corticosterone and luteinizing hormone in the plasma of the domestic hen.

Ovipositions in hens maintained under schedules of 16h light : 8h darkness (16L : 8D) or 8L: 16D were restricted to a 12h period of the day while in hens maintained on continuous light, ovipositions occurred at times throughout the whole of the 24h day. In hens maintained in continuous light a significant rise in the plasma concentration of corticosterone was observed 11-9h before ovulation/oviposition. In hens in 16L : 8D there was an increase in the concentration of corticosterone in the plasma during the first 1.5h of darkness which, under that schedule, coincides with the onset of the "open period" for the occurrence of the preovulatory release of LH. In hens ovulating the first egg of a sequence the rise in the secretion of corticosterone was only transient and levels fell as preovulatory concentrations of LH rose to a peak. However, in hens undergoing an ovulation late in a sequence or in those not expected to ovulate, the concentration of corticosterone in the plasma continued to rise to attain a maximal concentration 8h later. In hens maintained in 8L : 16D there was a tendency for the concentration of corticosterone in the plasma to increase at the beginning of the open period, 4 h after the onset of darkness, though this rise was much smaller than that observed at the beginning of the open period of hens on 16L : 8D. A further, more pronounced, increase in concentration of corticosterone was observed between 11 and 15h after the onset of darkness. It is suggested that the rise in the concentration of corticosterone at 11-9 h before ovulation in hens in continuous light reflects the beginning of an open period with a free-running circadian periodicity of 26-27 h.

Animals↗

Modification by metyrapone of the "open period" for pre-ovulatory lh release in the hen.

1. A single injection into laying hens of 60 mg metyrapone 28 h after the final ovulation of a sequence induced increases in the plasma concentrations of LH and progesterone, followed by premature ovulation. Injection of metyrapone 8 h after ovulation, however, did not affect plasma concentrations of either LH or progesterone. 2. Injection of laying hens with 60 mg metyrapone on 5 successive days reduced the effectiveness of exogenous ACTH in increasing the plasma concentration of corticosterone and abolished the system of "open" and "closed periods" for pre-ovulatory LH release. Thus, pre-ovulatory LH surges and ovipositions occurred throughout the 24-h day instead of being restricted to an 8 to 10-h period of the day. 3. These observations suggest that changes in environmental stimuli such as light act via the adrenal gland in regulating the timing of the "open period" for the pre-ovulatory release of LH in the hen.

Animals↗

Abrupt decrease in daylength and short-term changes in the plasma concentrations of FSH, LH and prolactin in anoestrous ewes.

The plasma concentrations of FSH, LH and prolactin in ewes were measured at frequent intervals during 24-h periods in anoestrus at different times from the onset of the breeding season. Ewes kept under natural daylength conditions were compared with ewes in which the onset of the breeding season was advanced by exposure to constant short days (8L : 16D). The concentrations of FSH during mid-anoestrus did not vary during the day and there was no effect of short days or any changes which could be associated with the onset of ovulation. In all of the ewes pulsatile releases of LH were observed on each sampling occasion. During mid-anoestrus the occurrence of LH pulses varied between 1 and 3/day and one of the pulses appeared to be synchronized with dawn. Exposure to short days did not affect the frequency of LH release. In both groups of ewes an increased frequency of LH pulses was observed in the period 12-14 days before the first ovulation but this was associated with a decrease in the magnitude of each pulse. Prolactin concentrations were raised during anoestrus and tended to be higher during the hours of darkness and in the early morning. Exposure to short days for 3 weeks abolished these diurnal changes and reduced the concentrations to non-detectable amounts.

Anestrus↗