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Biomedical subjects

D L Foster

Publications and source records attributed to D L Foster.

At least 19 recordsLinked to original sources
PubMed1992

Effect of nutritional repletion on pituitary and serum follicle-stimulating hormone isoform distribution in growth-retarded lambs.

Using nutritionally restricted ovariectomized lambs, we tested the hypothesis that nutritionally regulated endogenous increases in GnRH secretion (as assessed by LH pulsatility) not only alter the quantity of FSH present in the pituitary and serum, but also alter the pituitary and serum FSH isoform distribution. Eleven lambs were nutritionally restricted from weaning and ovariectomized at 12 wk of age. Beginning at 56 wk, 6 were fed ad libitum for 14 days, and the other 5 were continued on the restricted diet. Jugular blood samples were collected frequently (12-min interval) for 4 h prior to pituitary removal. Immunoreactive ovine LH (I-oLH) and immunoreactive ovine FSH (I-oFSH) concentrations were measured in sera and pituitary extracts. Bioactive (B) oFSH and I-oFSH isoform distribution patterns were determined in serum pools and pituitary extracts. Ad libitum feeding increased I-oLH pulsatility and mean concentrations of pituitary and serum I-oFSH and B-oFSH. The I-oFSH isoform distribution patterns in the pituitaries from the nutritionally restricted animals were not different from those of repleted lambs; in both, the predominant FSH peak eluted in the pH range of 3.5-5.6. A similar predominance of I-oFSH isoforms was also evident in the serum of ad libitum-fed animals. This predominance was not demonstrable in 3 of the restricted-fed animals due to low circulating concentrations of FSH (less than 2.5 ng/ml). Subsequent studies, utilizing serum from 4 additional restricted-fed lambs with circulating I-oFSH concentrations in the range of 4-14 ng/ml (but no detectable LH pulses) revealed similar predominance of oFSH isoforms in the pH 3.5-5.6 range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prenatal androgens and the timing of seasonal reproductive transitions in sheep.

Both the onset of puberty in the lamb and the annual resumption of reproductive activity in adult male and female sheep are characterized by increased secretion of LH due to reduced responsiveness to steroid inhibition. However, the timing of puberty is sexually differentiated, for males undergo a reduction in sensitivity to steroid feedback at 10 wk of age, whereas females remain highly responsive to steroid inhibition until 30 wk. This sex difference is determined by androgens in utero. The present study was conducted to determine whether a sex difference exists in the timing of seasonal transitions in adult males and females. We compared serum LH in gonadectomized, estradiol-treated males (n = 7), females (n = 6), and androgenized females (n = 5) from blood samples collected twice weekly for one year. As determined by changes in the pattern of LH secretion, the onset and termination of the autumn breeding season were not different between males, females, and androgenized females (termination: 1 February +/- 4 days, mean +/- SE all groups; onset: males, 22 August +/- 4 days; females, 5 September +/- 18 days; androgenized females, 16 September +/- 10.5 days). However, there was a transient increase in LH (20 May to 23 June) in males, but not in females or androgenized females. Although no effects of prenatal testosterone were evident in the control of LH secretion in adult androgenized females, LH secretion in androgenized males was elevated throughout the nonbreeding season in 3 of 5 animals, indicating that exogenous testosterone may reduce seasonal increases in responsiveness to steroid inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

GnRH neurons in the fetal lamb hypothalamus are similar in males and females.

The critical period for sexual differentiation of the brain of the developing lamb occurs before birth. Exposure to steroids during this sensitive period in midgestation alters the control of GnRH secretion after birth. The present study examined neurons immunolabeled for GnRH in male and female lambs during the critical period for sexual differentiation to determine if these neurons are sexually dimorphic. Neuron number, anatomical distribution, and the number of neuronal processes of GnRH-containing neurons from midgestation (85 days) male and female fetuses were compared (n = 5 each). Immunoreactive cells were labelled using LR-1 as the primary antiserum, followed by a biotinylated secondary antibody and the formation of an avidin-biotin-horseradish peroxidase (HRP) complex. The HRP was visualized histochemically using diaminobenzidine as the chromagen. GnRH neurons were localized in 60 microns coronal sections from the area of the diagonal band of Broca to the rostral mammillary bodies. The neurons were classified as unipolar, bipolar, or multipolar, according to the number of neuronal processes. The number of neuronal processes, the pattern of distribution, and the estimated total number of GnRH neurons in male and female fetuses was similar (p greater than 0.05). Furthermore, these parameters were equivalent to those reported for the adult female. These data indicate the GnRH neurosecretory system matures prior to midgestation in the sheep, and in a similar manner in males and females.

Animals↗
PubMed1992

Opioid inhibition of luteinizing hormone secretion compared in developing male and female sheep.

The sheep exhibits a marked sex difference in the timing of the pubertal increase in luteinizing hormone (LH). Male lambs undergo a reduction in sensitivity to inhibitory steroid feedback, leading to an increase in LH by 10 weeks of age, but females remain hypersensitive until 30 weeks of age. Endogenous opioids suppress LH secretion in the female lamb prepubertally and in adult male and female sheep. It has been suggested that a reduction in opioid inhibition of LH secretion is the signal to time puberty. Therefore, if a decrease in opioid tone occurs during sexual maturation, it should begin earlier in the male lamb than in the female. The objective of this study was to compare opioid inhibition of LH secretion in male and female lambs in relation to the timing of puberty. Our approach was to examine the response to the opioid antagonist naloxone at various ages in both sexes. To determine the timing of the pubertal LH rise in the presence of constant inhibitory steroid feedback, male and female lambs (n = 5 each) were gonadectomized at 3 weeks of age and implanted with a Silastic capsule of estradiol. They were then challenged with naloxone at 5, 11, and 23 weeks of age; blood samples were collected every 12 min for 8 hours, and lambs received naloxone (1 mg/kg i.v.) at hours 4, 5, 6, and 7. Mean LH before and during naloxone treatment was compared at each age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Circulating bioactive follicle-stimulating hormone and less acidic follicle-stimulating hormone isoforms increase during experimental induction of puberty in the female lamb.

The pubertal process with its multifaceted neuroendocrine control provides an excellent model for the study of the regulation of FSH heterogeneity. We tested the hypothesis that during the pubertal transition in the female lamb 1) an increase in both pituitary and circulating bioactive FSH concentrations occur and 2) that the increase in bioactivity is associated with a change in the distribution pattern of both pituitary and circulating FSH isoforms. Pituitary and serum immunoreactive (I), and bioactive (B, Sertoli cell bioassay) FSH concentrations were measured in six prepubertal lambs (18 +/- 1 weeks, 29.9 +/- 2.8 kg body weight; mean +/- SE) and compared to those of six others (24.2 +/- 2.2 weeks of age, 41.4 +/- 2.5 kg body weight) during the pubertal transition period. Puberty was synchronized by pulsatile iv administration of GnRH (2 ng/kg every 2 h for 24 h and then at hourly intervals for the next 12 h) in a manner mimicking the I-LH pulse patterns observed during the natural transition to adulthood. Blood samples were collected at 12-min intervals for 4 h from both groups of lambs; for the pubertal group this included the final 32-36 h of GnRH administration. At the end of the study, a 25 ml volume of peripheral blood was collected from both prepubertal and pubertal females for the determination of serum FSH distribution patterns; the lambs were then euthanised, and pituitaries were removed for determination of pituitary hormone content and FSH isoform distribution patterns. In addition, the distribution pattern of I-FSH isoforms in the pituitary and serum from both groups of lambs were compared. The pubertal stages of all lambs were verified by measuring the size of follicles, the circulating concentrations of estradiol (E2) and inhibin, and the I-LH pulse patterns. Prepubertal lambs had low frequency I-LH pulses, small (2-3 mm) size ovarian follicles and low circulating concentrations of E2 (4.1 +/- 0.4 pg/ml) and inhibin (38.0 +/- 2.9 U/ml WHO). By contrast, all the pubertal lambs had hourly I-LH pulse frequency (induced with exogenous GnRH), a large (5-6 mm) follicle (in one lamb a 4-mm follicle), follicular phase levels of E2 (7.1 +/- 0.8 pg/ml), and higher concentrations of inhibin (53.2 +/- 3.1 U/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Sex differences in nutritional modulation of gonadotropin secretion during development: studies in the growth-retarded lamb.

This study determined whether changes in nutrition during development alter LH secretion in males in a manner similar to that in females; sheep were used as an experimental model. Studies were conducted in the absence of gonadal steroid negative feedback. First, we compared the effect of chronic growth restriction on LH secretion in male and female lambs. Second, we determined whether the gonadotropic response to acute increases and decreases in nutrition is sexually differentiated. Seven male and 8 female Suffolk lambs, gonadectomized, and weaned by 8 wk of age were maintained at a target weight of 20 kg by level of nutrition. After 7 wk of chronic low nutrition (15 wk of age), LH pulse frequency was equally low in males (2.0 +/- 0.7 pulses/4 h) and females (2.0 +/- 0.4 pulses/4 h) relative to that (ca. hourly pulses) in normally growing gonadectomized lambs. Seven weeks later, at 22 wk of age, LH pulse frequency dropped further (males 0.9 +/- 0.3/4 h; females 0.9 +/- 0.4 pulses/4 h). The results of this first experiment, in which we observed no sex difference in gonadotropin secretion under chronic growth restriction, imply equal neuroendocrine sensitivity in males and females to long-term low nutrition. In the second experiment, however, a sex difference was evident in the response to increased and decreased nutrition. Both sexes responded to feeding ad libitum with a rapid increase in LH pulse frequency, but the response was greater in the males than in the females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1991

Postpubertal maturation of endogenous opioid regulation of luteinizing hormone secretion in the female sheep.

This study investigated whether the role of endogenous opioid peptides in the suppression of LH secretion during seasonal anestrus in the sheep changes with age. The experimental approach was to determine the effect of blockade of opioid receptors with naloxone on LH secretion at different times of year within the anestrous season, and to compare responses between seasonally anestrous sheep of different ages. Sheep, all past the normal age of puberty, were ovariectomized before the study and treated s.c. with estradiol implants to provide a fixed estradiol feedback signal. One-year-old females responded to naloxone with a rapid increase in LH pulse frequency in the early (April) and late (August) phases of their first anestrous season. This response was similar to that previously found in prepubertal female sheep. Only 5 of the 8 females responded to the same naloxone challenge in mid anestrus (June), suggesting that the contribution of opioid pathways to the inhibition of LH secretion at this time of year is not necessarily the same as that in early and late anestrus. None of the older anestrous sheep (greater than or equal to 2 yr) responded to naloxone in June, indicating age-related changes in the role of endogenous opioid mechanisms in the inhibition of LH secretion. Ovary-intact mature sheep did not respond to naloxone, in contrast to our previous observations in intact prepubertal females. We infer that the neural mechanisms underlying the superficially similar hypogonadotropic states that occur during the prepubertal period, first anestrous season, and later anestrous seasons are not identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

The timing of neuroendocrine sexual maturity in the male lamb by photoperiod.

In spring-born female lambs, the long days of summer, followed by their gradual decrease, provide the seasonal cue necessary to time puberty to early autumn (approximately 30 wk of age). Male lambs begin spermatogenesis during mid-summer, some 20 wk before puberty occurs in females. Unlike young female lambs, male lambs attain puberty at the same age under a variety of photoperiodic manipulations, raising the possibility that sexual maturation in males is not affected by photoperiod. We have reinvestigated the role of photoperiod on puberty in the male lamb, using a more precise indicator of reproductive activation--the decreased sensitivity of the hypothalamo-pituitary axis to inhibitory steroid feedback leading to increased LH secretion. To test whether photoperiod can influence the onset of neuroendocrine sexual maturation in male lambs, this study compared the timing of the decrease in sensitivity to inhibitory steroid feedback in two groups of males under opposite photoperiodic conditions. Eight males were reared indoors from 2 wk of age under conditions simulating the natural increasing and decreasing day lengths around the summer solstice; an additional 7 males were exposed to a reversed simulated natural photoperiod in which the changes in day length were amplified and accelerated relative to outdoor conditions. Both groups of lambs were castrated and received s.c. implants of Silastic estradiol capsules to provide a constant steroid feedback signal. The timing of reduction in sensitivity to estradiol negative feedback, measured as a sustained increase in circulating of LH above 1.0 ng/ml, was used to define neuroendocrine sexual maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Patterns of circulating gonadotropins and ovarian steroids during the first periovulatory period in the developing sheep.

This report provides evidence that an increment in serum gonadotropin levels occurs at puberty in the sheep and that this reflects the critical hormonal event culminating in first ovulation in this species. Blood samples were collected from 6 female lambs at 4-h intervals for a period of approximately 2 mo around the expected time of puberty (32 wk of age) until behavioral estrus was observed and ovulation was verified by assay of serum progesterone. Patterns of circulating LH, FSH, progesterone, and estradiol concentrations were characterized during the peripubertal period for each lamb. A rise in serum levels of both LH and FSH began approximately 7-10 days before the first preovulatory surge of gonadotropins. Although the increase in gonadotropin levels occurred gradually over several days, serum estradiol levels rose only during the final 40-60 h prior to the preovulatory surge of gonadotropin. Serum progesterone profiles revealed, however, that normal (14-16-day) luteal phases were induced in only 2 of 6 females as a result of the first surge. In four lambs, a short luteal phase of 2.5 days' duration occurred, which was followed by another estradiol rise and a preovulatory surge that then resulted in a full luteal phase of 14 days' duration. These data demonstrate clearly that the precipitating event at puberty in the female sheep is an increase in circulating gonadotropin levels and that the estradiol secreted from the newly stimulated follicle provides the signal for the first preovulatory surge.

Animals↗
PubMed1991

Prenatal androgens time neuroendocrine sexual maturation.

The present study determined whether exposure to gonadal steroids in utero dictates the postnatal control of gonadotropin secretion in the lamb. There is a marked sex difference in the timing of neuroendocrine sexual maturation in sheep; while male lambs undergo a reduction in sensitivity to inhibitory gonadal steroid feedback by 10 weeks of age, females remain hypersensitive until 30 weeks. The hypothesis was tested that prenatal androgens advance the time of the decrease in feedback sensitivity, and hence the pubertal increase in pulsatile gonadotropin secretion. Pregnant ewes were injected each week with 100 mg testosterone cypionate im from 30-90 days of gestation (term is approximately 150 days). Five female lambs were born with masculinized external genitalia (penis and scrotum). These females, together with eight androgenized males, eight control males, and eight control females, were gonadectomized at 2 weeks of age and implanted with a Silastic capsule of estradiol to produce a constant steroid feedback signal. Blood samples were collected twice weekly to monitor trends in LH secretion. For determination of LH pulse frequency, samples were collected frequently (every 12 min for 4 h) at various intervals between 5 and 32 weeks of age. In males, a sustained increase in LH from biweekly blood samples, indicative of reduced sensitivity to inhibitory steroid feedback, began at 10.1 +/- 1.4 weeks (mean +/- SE) of age in control males and at 5.4 +/- 0.1 weeks in androgenized males. By contrast, control females remained hypersensitive much longer as evidenced by the delay in the LH rise until 27.2 +/- 0.8 weeks. The response of the five androgenized females was intermediate; LH increased at 4, 7, 16, 20, and 21 weeks of age with an early increase of LH being associated with more pronounced masculinization of the genitalia. Patterns of pulsatile LH secretion reflected differences in serum LH measured from biweekly blood samples. For example, at 20 weeks of age, before the pubertal LH rise in female lambs, no pulses were evident in control females, whereas LH pulse frequency averaged 1.6 +/- 0.7 pulses/4 h in androgenized females. At this age, postpubertal males had 2.8 +/- 0.5 LH pulses/4 h. These results lead to the conclusion that in the sheep, prenatal androgens can masculinize patterns of gonadotropin secretion, and that the timing of reproductive neuroendocrine maturation after birth is programmed by androgens in utero.

Androgens↗
PubMed1991

Metabolic interfaces between growth and reproduction. IV. Chronic pulsatile administration of growth hormone and the timing of puberty in the female sheep.

Puberty in the female lamb is accompanied by an increased frequency of LH pulses, and during normal development this is preceded by a decline in GH. Conversely, in the growth-retarded lamb, when LH levels are depressed by low nutrition, GH secretion is elevated. Based upon this inverse relationship, we tested the hypothesis that GH may act as a metabolic signal from the brain to inhibit the secretion of LH, and that the decline in GH times puberty. Our approach was to extend high circulating GH levels far beyond the early postnatal period, in a physiological pattern and level, in an attempt to block the pubertal LH rise. To evaluate the pattern of LH as a continuous variable under conditions of constant estradiol negative feedback, the gonadotropin was measured in blood samples collected by jugular venipuncture twice weekly; the lambs were ovariectomized and treated chronically with estradiol (Silastic capsule) beginning at 3 weeks of age. Nine lambs served as untreated controls, and 7 were infused iv with pituitary-derived bovine GH (bGH) between 5 and 28 weeks of age. A programmable backpack infusion pump delivered bGH as hourly pulses, with a total dose of 18 micrograms/kg.24 h, to maintain a physiological pattern and level of GH. At various ages, blood samples were collected at 12-min intervals for 6 h to monitor patterns and levels of peripheral LH and GH. Circulating GH in untreated and treated lambs averaged 7.7 +/- 1.5 ng/ml over a 6-h period at 4 weeks of age and declined to 1.1 +/- 0.2 ng/ml by 19 weeks in the untreated lambs; in contrast, bGH-infused lambs averaged 10.4 +/- 0.9 ng/ml at 19 weeks. Although body weights did not differ, back fat depth and quantity of perirenal fat were reduced in bGH-treated females compared to that in controls. Moreover, insulin-like growth factor-I levels were higher in bGH-treated compared with control lambs, and the bGH-treated lambs exhibited glucose intolerance, thus confirming that infused bGH was biologically active. Neuroendocrine sexual maturity, however, was not different in bGH-treated and control lambs, and it occurred at 21-22 weeks of age. The results do not support our hypothesis that decreasing GH secretion is a requirement for puberty in the sheep. Moreover, unlike in children with delayed puberty, exogenous bGH did not advance normal puberty in the lamb.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Influence of food intake but independence of body weight on puberty in female sheep.

The effect of maintaining female sheep at a body weight intermediate between the normal weight for puberty (30-35 kg) and 20 kg (puberty suppressed) on the onset of oestrous cycles was studied. In addition, the influence of ad-libitum food intake or insulin infusion was studied in animals previously maintained at 20 kg. Coopworth ewe lambs (10 weeks old) were allocated to one of 6 treatments: (A) ad-libitum fed (n = 6), (B) ad-libitum fed to 28 kg then maintained at that weight (n = 6), (C) ad-libitum fed to 24 kg then maintained at that weight (n = 6), (D) maintained at 20 kg until Week 29 and then fed ad libitum (n = 6), (E) maintained at 20 kg and infused with 0.1 U insulin/kg/24 h for 2 weeks from 29-31 weeks of age (n = 5), (F) maintained at 20 kg (n = 6). The lambs were penned indoors under natural photo-period, which was decreasing virtually throughout the study, and fed a pelleted concentrate diet which was recorded daily. They were blood sampled twice a week, and plasma was analysed for progesterone. Puberty was defined as the date when plasma concentrations of progesterone first exceeded 1 ng/ml. In addition, ewes in Groups D, E and F were blood sampled every 10 min for 8 h on Days 0 and +12 of the insulin infusion or access to ad-libitum feeding and the plasma was analysed for luteinizing hormone (LH).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Pulsatile LH secretion during sexual maturation in the female sheep: photoperiodic regulation in the presence and absence of ovarian steroid feedback as determined in the same individual.

This study in the female lamb determined if photoperiod influences pulsatile LH secretion before puberty. Moreover, we reevaluated the hypothesis that the photoperiod-modulated decrease in responsiveness to ovarian steroid inhibition which results in increased pulsatile LH secretion during sexual maturation reflects an increase in direct central nervous system 'drive' of gonadotropin secretion. The experimental approach was to monitor pulsatile LH secretion in the presence and absence of estradiol negative feedback during development in the same individuals. This was accomplished by the periodic replacement and removal of constant-release estradiol capsules every 3 weeks in ovariectomized lambs (OVX) which were raised in photoperiods that delay or permit normal puberty. A new algorithm was used for identification of episodes of LH secretion. In OVX lambs in the permissive sequence of photoperiods (long days of 16L:8D until 18 weeks of age, followed by short days of 8L:16D), LH pulse frequency was low in the presence of estradiol early in life at 9 weeks of age, but increased at later ages. LH pulse frequency in the presence of estradiol feedback was not associated with that in the absence of estradiol replacement. LH pulse frequency was high throughout development in the absence of estradiol and increased further at the time when responsiveness to estradiol negative feedback decreased. In lambs raised in the inhibitory sequence of photoperiods (short days until 18 weeks of age followed by long days), LH pulse frequency in the presence of estradiol remained low throughout the duration of the experiment, but in the absence of estradiol, LH pulse frequency increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Sexual differentiation of the mechanism controlling pulsatile secretion of luteinizing hormone contributes to sexual differences in the timing of puberty in sheep.

Sexual differences in the regulation of tonic luteinizing hormone (LH) secretion were examined in immature female and male sheep (eight each, including six pairs of female/male twins). After gonadectomy of lambs at 2 weeks of age, Silastic capsules filled with estradiol, a primary central feedback steroid in both females and males, were implanted every 3 weeks for 3 days, and then removed, so that the pattern of LH secretion could be repeatedly determined in the same individuals both with and without steroid feedback. Implanted capsules yielded circulating steroid levels of 2-5 pg/ml. Circulating LH concentrations were determined by radioimmunoassay in blood samples collected at 12-min intervals for 4 h immediately before estradiol was implanted, and again, immediately before it was removed 3 days later. In male lambs, a decrease in responsiveness of the hypothalamic-pituitary axis to inhibition by estradiol began at 8-11 weeks, as evidenced by the progressive increase in mean LH concentrations and frequency of LH pulses. This correlated temporally with the onset of spermatogenesis in intact male controls (n = 8). In females, a similar decrease in responsiveness did not occur until 26-29 weeks of age, corresponding to the onset of ovulatory cycles in intact female controls (n = 6). In the absence of estradiol implants, LH pulse frequencies were higher in male lambs than in female lambs between 5 and 35 weeks of age. There was no further increase in LH pulse frequency in the absence of the gonads in either sex during the pubertal period. These findings suggest that the mechanism regulating tonic LH secretion in developing lambs is sexually differentiated in its responsiveness to inhibition by estradiol. This differentiation also occurs at a more fundamental steroid-independent level, but any causal relationship between the higher steroid-independent LH pulse frequency and the lower responsiveness to estradiol negative feedback in males is not evident. We hypothesize that these sexual differences in the regulation of tonic LH underlie the difference in the timing of puberty in male and female lambs.

Aging↗
PubMed1990

Metabolic interfaces between growth and reproduction. III. Central mechanisms controlling pulsatile luteinizing hormone secretion in the nutritionally growth-limited female lamb.

Growth retardation induced by dietary restriction in the lamb results in a low frequency of episodic LH secretion and, thus, delayed puberty. Such lambs respond normally to physiological doses of GnRH, indicating that the pituitary gland can function adequately during diet-induced hypogonadotropism. The current studies investigated central mechanisms underlying diet-induced hypogonadotropism. The first aim was to determine whether the hypothalamic GnRH secretory system is capable of normal function. The initial approach was to compare hypothalamic GnRH content between lambs on a restricted diet with low LH pulse frequency (less than 1 pulse/4 h; n = 5) and lambs on an ad libitum diet with high LH pulse frequency (4.5 +/- 0.4 pulses/4 h; n = 5). RIA of extracts of preoptic area and mediobasal hypothalamus/median eminence tissue blocks revealed no differences in GnRH content between lambs on a restricted diet and those on an ad libitum diet. The second approach was to determine if LH secretion could be induced by chemical stimulation of neuronal function with N-methyl-D,L-aspartate (NMA), an excitatory amino acid agonist. Initially, a single iv bolus of NMA was given to hypogonadotropic lambs on a restricted diet. There was a dose-dependent immediate rise in serum LH concentrations. All lambs responded to the highest dose (5.0 mg/kg BW; n = 6), and four of five lambs responded to the intermediate dose (1.0 mg/kg). No lambs responded to the lowest dose (0.2 ng/kg), despite a normal response to GnRH (2.5 ng/kg BW, iv). In a second experiment, hypogonadotropic lambs on a restricted diet were treated with repeated injections of NMA (5 mg/kg BW, iv) at either hourly intervals (n = 6) or every 3 h (n = 6). Each NMA injection induced a LH pulse in both treatment regimens over the entire 7-h experimental period. Thus, the nutritionally growth-limited lamb is capable of sustained production of LH pulses, which, we presume, reflect GnRH secretion. The second aim was to test the hypothesis that endogenous opioid mechanisms inhibit LH secretion during nutritionally induced hypogonadotropism, because opioid pathways are a poor inhibitory regulator of LH secretion in the normally developing sheep, even in the absence of ovarian steroids. We were unable to detect any effects of the opiate antagonist naloxone on LH secretion in the nutritionally growth-limited lamb. We conclude that central mechanisms controlling the release, rather than synthesis, of GnRH are limiting LH secretion when sexual maturation is delayed by growth retardation. Moreover, opioid inhibition is not the primary reason for hypogonadotropism during dietary restriction.

Animals↗