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Biomedical subjects

D L Foster

Publications and source records attributed to D L Foster.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Pineal melatonin rhythms and the timing of puberty in mammals.

The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknown. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.

Animals↗

Amplitude modulation of the nightly melatonin rise in the neonatal lamb and the subsequent timing of puberty.

Spring-born female lambs require a decrease in day length for the normal timing of puberty the following autumn. If this decrease occurs early in postnatal life (i.e. 0-10 weeks), puberty is delayed. This study tested the hypothesis that failure of the neonatal lamb to respond to the critical long-day to short-day signal is due to inadequate nocturnal melatonin secretion. The approach was to artificially increase, to adult levels, the low nighttime rises of melatonin during the early postnatal period. Eight female lambs served as controls; they were raised on short days until 17 wk of age, and then exposed to 5 wk of long days, after which they were returned to short days. This alternating sequence of photoperiods during mid-development would be expected to induce normal puberty. Sixteen experimental females were exposed to the critical block of long days much earlier; they were placed in long days between 2 and 7 wk of age and in short days thereafter. Half (n = 8) received no further treatment. The other half (n = 8) were infused nightly with melatonin during the 8-h dark phase of the 5-wk, long-day photoperiod. This increased the amplitude of the natural nighttime melatonin rises 3- to 4-fold, well into the adult range.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Entrainment of the melatonin rhythms in early postnatal lambs and their mothers.

Although the developing sheep can produce an appropriately timed melatonin rhythm as early as 1 week after birth, it is not known whether the lamb is able to adjust its melatonin rhythm to a change in daylength. The ability of the young lamb to entrain its pattern of melatonin secretion to a new photoperiod was determined in the present study. Eight female lambs and their mothers were raised in long days (LD 16:8) beginning 2 weeks postpartum. At 7 weeks of age, the time of lights-off was advanced 8 hr, the short-day photoperiod then being LD 8:16; the time of lights-on remained unchanged. Concentrations of melatonin were measured in blood samples collected hourly on days - 1, 0, 2, 4, 6, and 13 relative to the light change. On day 0, all mothers and daughters had advanced the onset of melatonin secretion by at least 1 hr, and by day 13, 12 of 16 had completely entrained to the new photoperiod. The rate of entrainment among individuals varied; the mean rate for lambs and mothers did not differ. This study provides evidence that the melatonin-rhythm-generating system matures shortly after birth.

Analysis of Variance↗

The ontogeny of melatonin secretion in the lamb.

In the female lamb, early postnatal photoperiod treatments do not alter the timing of puberty as do treatments at later ages. In the male lamb, early photoperiod treatments also fail to influence reproductive development. This prompted the hypothesis that the very young lamb may be unable to transduce changes in daylength into appropriate endocrine cues for puberty. The hypothesis was evaluated by determining the ontogeny of pineal melatonin secretory patterns in both female (n = 4-6) and male (n = 4) lambs under natural photoperiods. Serum melatonin concentrations were determined by a modified RIA in samples collected hourly for 24 or 48 h. Clustering analysis was used to define elevated and nonelevated periods of melatonin secretion. Elevated secretion was evident at night in six of eight lambs by 1 week of age and in all lambs by 3 weeks of age. In nearly all cases, the elevated nighttime levels accurately and consistently reflected the duration of the dark period. The mean amplitude of the elevated nighttime melatonin secretion was low in very young lambs and increased with age. No difference between females and males was observed in either the amplitude or duration of the nocturnal melatonin rise. Our results do not support the hypothesis that the failure of early photoperiod treatments to influence reproductive development is due to an inability of the young lamb to transduce photoperiod patterns into an endocrine signal. Rather, they suggest that some other aspect of reproductive neuroendocrine function is restrictive at these ages.

Animals↗

Metabolic interfaces between growth and reproduction. I. Nutritional modulation of gonadotropin, prolactin, and growth hormone secretion in the growth-limited female lamb.

The acute and long term effects of dietary restrictions on gonadotropin secretion were studied in ovariectomized female lambs. Nutritionally growth-restricted lambs which were chronically maintained at a body weight comparable to that at weaning (approximately 20 kg) became hypogonadotropic, exhibiting a low frequency of episodic LH discharges. Repeated administration of physiological doses of GnRH to these females at hourly intervals produced corresponding LH pulses, leading to the hypothesis that the dietary-induced hypogonadotropism arises from a deficiency in endogenous GnRH release, rather than an inability of the pituitary gland to secrete gonadotropins in response to hypothalamic stimulation. In such growth-restricted females receiving a single meal daily, initiation of ad libitum feeding led to a spontaneous LH pulse within 1 h. After 14 days of increased food intake, hourly LH pulses were evident; a marked reduction in LH pulse frequency was associated with the return to limited nutrition. No effects on pulse amplitude were evident. Changes in circulating FSH followed a pattern similar to that for LH, namely an increase in concentration with improved nutrition and a decrease with reduced nutrition. The rate of response of FSH secretion to these alterations in nutrition was slower than that for LH. PRL levels were not altered by changes in nutrition, and a clear annual rhythm of secretion was observed. GH concentrations changed inversely with the level of nutrition; high secretion was associated with periods of restricted feeding, and low secretion with increased nutrition. These findings indicate that dietary restriction in the developing female lamb depresses gonadotropin secretion without reducing other anterior pituitary gland secretions, such as PRL and GH. That these changes occur in the absence of the ovaries implies that metabolic and growth-related modulation of neuroendocrine function can occur independently of changes in sensitivity to the feedback actions of ovarian steroids and polypeptides.

Animal Nutritional Physiological Phenomena↗

Metabolic interfaces between growth and reproduction. II. Characterization of changes in messenger ribonucleic acid concentrations of gonadotropin subunits, growth hormone, and prolactin in nutritionally growth-limited lambs and the differential effects of increased nutrition.

Previous studies show that limited nutrition in the ovariectomized lamb results in an impairment of LH and FSH secretion, a phenomenon that is rapidly reversible by increasing the level of nutrition and independent of ovarian steroid feedback. The present study characterizes the biosynthesis of pituitary hormones in the nutritionally growth-limited female lamb by measuring steady state mRNA concentrations. These changes were examined relatively to pituitary and serum hormone concentrations to establish the relationship(s) of synthesis and secretion in response to nutritional manipulation. Ad libitum feeding of nutritionally growth-restricted ovariectomized lambs for 14 days resulted in an increase in the frequency of episodic LH release, thereby increasing mean serum LH concentrations (P less than 0.001). Similarly, mean circulating concentrations of FSH were increased (P less than 0.001). By contrast, serum GH concentrations were lowered significantly as a result of ad libitum feeding (P less than 0.05). Serum PRL concentrations remained unchanged. Although pituitary LH and PRL concentrations were also unchanged in response to increased nutrition feeding, FSH and GH concentrations increased (P less than 0.05). Short-term ad libitum feeding of the chronically food-restricted lamb resulted in significant changes in mRNA concentrations for all hormones except PRL. The concentrations of gonadotropin subunit mRNAs (i.e. alpha, LH beta, and FSH beta) were all significantly higher in response to increased nutrition (P less than 0.001). GH mRNA was also affected; however, feeding decreased concentrations (P less than 0.001). The results demonstrate that an increase in the level of nutrition in the restricted diet lamb produces profound changes in the synthesis, storage, and secretion of LH, FSH, and GH. These changes appear to be coordinated, although the response differs depending upon the hormone.

Animal Nutritional Physiological Phenomena↗

Endogenous opioid regulation of pulsatile luteinizing hormone secretion during sexual maturation in the female sheep.

The developing female sheep, which attains puberty after 25 weeks of age, was used as an experimental model to investigate the role of endogenous opioid peptides in the control of pulsatile LH secretion during sexual maturation. Treatment of ovary-intact prepubertal sheep at 12 weeks of age with the opiate antagonist naloxone resulted in a dose-dependent increase in LH secretion. Subsequent studies used ovariectomized (OVX) lambs implanted with capsules containing 17 beta-estradiol to provide a constant, ovarian steroid feedback signal throughout development. Naloxone treatment (hourly iv injections of 1 mg/kg BW for 4 h) produced an increase in the frequency of episodic LH secretion at all prepubertal ages, when lambs were highly sensitive to the estradiol negative feedback. However, increases in LH pulse frequency were also induced by naloxone treatment at a postpubertal age in estradiol-treated OVX sheep, indicating that opioid inhibition is still present at a time when sensitivity to the feedback effects of ovarian steroids is markedly reduced and endogenous LH secretion is increased. These observations in ovary-intact and estradiol-treated OVX lambs suggest that opioid mechanisms inhibit pulsatile tonic LH secretion during both the prepubertal and postpubertal periods. Endogenous opioid inhibition of LH secretion is not dependent on the presence of ovarian steroids, as evidenced by the response to naloxone 3 weeks after removal of an estradiol implant from OVX lambs, when LH pulse frequency was already high. Naloxone treatment increased LH pulse frequency further, at both a prepubertal age (18 weeks) and a postpubertal age (38 weeks). Naloxone also increased LH pulse frequency in OVX lambs in which LH secretion was inhibited chronically by progesterone rather than by estradiol. The response to naloxone was similar in postpubertal P-treated OVX lambs and age-matched prepubertal P-treated OVX controls in which puberty had been delayed by means of an inhibitory seasonal photoperiod. In addition, after removal of steroid implants to allow LH secretion to increase, the degree of inhibition of LH secretion by the opiate agonist morphine was similar between age-matched postpubertal sheep and those with photoperiodically delayed puberty. We conclude that endogenous opioid mechanisms are an important inhibitory mechanism controlling pulsatile LH secretion in the developing sheep. However, changes in opioid inhibition are unlikely to underlie the decrease in sensitivity to steroid negative feedback and increase in pulsatile LH secretion that occur at puberty.

Animals↗

Prenatal photoperiod influences neonatal prolactin secretion in the sheep.

This study tested the hypothesis that the fetal sheep can respond to photoperiod cues. Pregnant Suffolk ewes were maintained in artificial photoperiod of either long days [16 h of light, 8 h of dark (16L:8D)] or short days (8L:16D) from approximately 100 days of gestation until term at approximately 147 days. On the day of birth, all lambs and their mothers were transferred to an intermediate photoperiod of 12L:12D; both groups were housed together. To provide an index of response to photoperiod, serum PRL concentrations were measured in blood samples collected daily 3-4 h after lights on. In lambs (n = 8 male; n = 7 female) born to mothers on long days, serum PRL concentrations were high (greater than 200 ng/ml) for the first few days after birth, but fell rapidly to low levels (less than 50 ng/ml) within 14 days postnatally in 12L:12D. Conversely, lambs (n = 8 male; n = 7 female) born to mothers on short days initially had low PRL concentrations, but these gradually increased in the postnatal 12L:12D photoperiod to 150 ng/ml by 32 days of age. Thus, serum PRL concentrations in lambs at birth reflect the photoperiodic treatment of their mother, and the subsequent PRL response to an intermediate photoperiod of 12L:12D depends on the photoperiodic history received in utero. We infer from these findings that the fetal lamb receives and responds to information about day length in utero and begins developing a seasonal photoperiod history before birth.

Animals↗

Bioactive follicle-stimulating hormone release in nutritionally growth-retarded ovariectomized lambs: regulation by nutritional repletion.

The nutritionally growth-retarded ovariectomized lamb provides a model system to investigate the regulation of immunoreactive and bioactive FSH release in the absence of feedback effects of ovarian products. We examined the acute effects of nutritional repletion on FSH release in this model. Five March-born lambs were weaned at 7 weeks of age and placed on a limited diet. All were ovariectomized at 31 weeks. At 37 weeks, they were fed ad libitum for 14 days. Blood samples were collected at 12 min intervals for 4 h on day -1 (restricted) and days 2, 7, and 14 of ad libitum feeding, and serum FSH concentrations were measured by both RIA and a Sertoli cell aromatase in vitro bioassay. Mean concentrations of serum immunoreactive FSH (I-FSH) and the bioactive FSH (B-FSH) increased 2- and 3-fold, respectively, after ad libitum feeding for 14 days. Pulse analyses by two objective computerized programs, DETECT and CLUSTER, revealed the presence of FSH pulses (predominantly B-FSH) during the restricted phase, as well as ad libitum fed phases, at times where I-LH pulses were not detected. In contrast to the increases in I-LH pulse frequency during ad libitum fed states, FSH pulse frequency remained stable whereas pulse amplitude increased. In addition, the overall B-FSH pulse amplitudes were 57 +/- 7% (mean +/- SE of three different pulse analyses) greater than I-FSH pulse amplitudes, implying preferential enrichment of FSH bioactivity. The results suggest that the mechanisms governing both the quantitative and qualitative changes in circulating FSH concentrations are extremely sensitive to changes in level of nutrition. The asynchronous occurrence of FSH pulses in the absence of I-LH pulses suggests that FSH may be more sensitive to small changes in GnRH secretion than I-LH, or that a hypothalamic releasing factor specific for FSH may be released.

Animals↗

Timing of puberty by photoperiod.

Photoperiod cues play an important role in the timing of puberty in the female lamb. Removal and replacement of photoperiod cues by denervation of the pineal gland and timed melatonin infusions, respectively, indicate that the pathway for transmission of photoperiod information develops well before puberty. This is reinforced by manipulation of artificial photoperiods during various periods of development. Such approaches reveal that even in the first few weeks of life, the pattern of melatonin secretion accords with daylength and modulates prolactin secretion. Several months later, after internal, growth-related cues indicate that sufficient body size has been achieved to initiate reproduction, photoperiod history is used as an important predictor of reproductive success, and thus, whether puberty should occur. In the female spring-born lamb, the decrease in daylength in autumn is the critical cue for the initiation of estrous cycles. Experimentally, this may be achieved by surgically disrupting the pathway for transmission of photic cues after appropriate long-day exposure. In the autumn-born lamb and in the slowly growing lamb, sexual maturation may be masked by the transition into seasonal anestrus the following spring. In these young females, a decreasing photoperiod or "removal of long days" (surgical) is not necessary for puberty the following autumn. Sufficient photoperiod history may be acquired in such lambs that they enter puberty as a consequence of becoming refractory to the long days of summer. We hypothesize that the phenomenon of refractoriness reflects the expression of an innate rhythm of reproductive activity and that changes in daylength experienced early in life serve to synchronize this rhythm with the seasonal environment.

Animals↗