Androgen negative feedback during the early rise in LH secretion in bull calves

1995 ◽  
Vol 145 (2) ◽  
pp. 243-249 ◽  
Author(s):  
N C Rawlings ◽  
A C O Evans

Abstract A transient elevation in mean circulating concentrations of LH and FSH occurs in the young bull calf prior to 24 weeks of age. The functional significance of this is not clear. To see if changes in the ability of androgens to suppress gonadotrophin secretion were involved in the start of this early rise in LH secretion or the cessation of the early rise in LH and FSH secretion, bull calves were treated with flutamide (androgen receptor blocker; n=5; 9 mg flutamide/kg body weight in propylene glycol (i.m./s.c.) in three equal portions at 12-h intervals) at 8, 16 and 24 weeks of age and bled every 15 min for 12 h beginning after the third flutamide treatment; control bulls received vehicle at these times. Control bulls (n=5) were bled every 15 min for 12 h at 4, 8, 12, 16 and 24 weeks of age, and all bulls were bled weekly. Serum samples were assayed for concentrations of LH, FSH and testosterone. Based on weekly and intensive bleedings for control and flutamide-treated bulls, an early rise in LH (8–18 weeks of age) and FSH (4–24 weeks of age) secretion was seen in all bull calves (P<0·05). At 8 weeks of age flutamide treatment resulted in increased mean serum LH concentrations (P<0·05); at 16 weeks of age it resulted in increased basal and mean LH concentrations and increased LH pulse frequency (P<0·05); and at 24 weeks of age in increased mean LH concentrations, LH pulse frequency and amplitude (P<0·05) in comparison with control bulls. Flutamide treatment resulted in decreased FSH pulse amplitude at 8 weeks of age and increased mean serum concentrations of FSH and FSH pulse frequency at 24 weeks of age (P<0·05). In flutamide-treated bull calves testicular growth was greater and sexual maturity was reached earlier than in control bull calves (P<0·05). We conclude that a reduced suppression of LH secretion by androgens does not appear to be a major contributing factor to the onset of the early increase in LH secretion, but increased suppression may be involved in the termination of the early rise of both LH and FSH secretion in the bull calf. The early increase in LH secretion may be a critical initial step in postnatal reproductive development, since flutamide treatment increased early LH secretion and resulted in earlier attainment of sexual maturity. Journal of Endocrinology (1995) 145, 243–249

Reproduction ◽  
2000 ◽  
pp. 159-167 ◽  
Author(s):  
JP Aravindakshan ◽  
A Honaramooz ◽  
PM Bartlewski ◽  
AP Beard ◽  
RR Pierson ◽  
...  

The reproductive development of bull calves born in spring and autumn was compared. Mean serum LH concentrations in calves born in spring increased from week 4 to week 18 after birth and decreased by week 24. In bull calves born in autumn, mean LH concentrations increased from week 4 to week 8 after birth and remained steady until week 44. LH pulse amplitude was lower in bull calves born in autumn than in calves born in spring until week 24 of age (P < 0.05). There was a negative correlation between LH pulse frequency at week 12 after birth and age at puberty in bull calves, irrespective of season of birth, and LH pulse frequency at week 18 also tended to correlate negatively with age at puberty. Mean serum FSH concentrations, age at puberty, bodyweight, scrotal circumference, testes, prostate and vesicular gland dimensions, and ultrasonographic grey scale (pixel units) were not significantly different between bull calves born in autumn and spring. However, age and body-weight at puberty were more variable for bull calves born in autumn (P < 0.05). In a second study, bull calves born in spring received either a melatonin or sham implant immediately after birth and at weeks 6 and 11 after birth. Implants were removed at week 20. Mean LH concentrations, LH pulse frequency and amplitude, mean FSH concentrations and age at puberty did not differ between the two groups. No significant differences between groups in the growth and pixel units of the reproductive tract were observed by ultrasonography. In conclusion, although there were differences in the pattern of LH secretion in the prepubertal period between bull calves born in autumn and spring, the postnatal changes in gonadotrophin secretion were not disrupted by melatonin treatment in bull calves born in spring. Reproductive tract development did not differ between calves born in spring and autumn but age at puberty was more variable in bull calves born in autumn. LH pulse frequency during the early prepubertal period may be a vital factor in determining the age of bull calves at puberty.


1991 ◽  
Vol 131 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Q. Dong ◽  
R. M. Lazarus ◽  
L. S. Wong ◽  
M. Vellios ◽  
D. J. Handelsman

ABSTRACT This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1–1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P=0·001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feed-back. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss. The impaired pituitary responsiveness to GnRH is at least partly involved in the reduction of LH pulse amplitude. Journal of Endocrinology (1991) 131, 49–55


1993 ◽  
Vol 128 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Lise Duranteau ◽  
Philippe Chanson ◽  
Joelle Blumberg-Tick ◽  
Guy Thomas ◽  
Sylvie Brailly ◽  
...  

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.


Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4249-4258 ◽  
Author(s):  
Casey C Nestor ◽  
Lique M. Coolen ◽  
Gail L. Nesselrod ◽  
Miro Valent ◽  
John M. Connors ◽  
...  

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.


Reproduction ◽  
1997 ◽  
Vol 111 (1) ◽  
pp. 41-50 ◽  
Author(s):  
R. K. Chandolia ◽  
A. Honaramooz ◽  
P. M. Bartlewski ◽  
A. P. Beard ◽  
N. C. Rawlings

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3368-3375 ◽  
Author(s):  
Jeremy T. Smith ◽  
I. Ross Young ◽  
Johannes D. Veldhuis ◽  
Iain J. Clarke

GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary-disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.


1992 ◽  
Vol 134 (1) ◽  
pp. 115-125 ◽  
Author(s):  
R. Webb ◽  
G. Baxter ◽  
D. McBride ◽  
A. S. McNeilly

ABSTRACT Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles >6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion. Journal of Endocrinology (1992) 134, 115–125


1995 ◽  
Vol 147 (3) ◽  
pp. 565-579 ◽  
Author(s):  
M L Barker-Gibb ◽  
C J Scott ◽  
J H Boublik ◽  
I J Clarke

Abstract Neuropeptide Y1–36 (NPY1–36) acts through Y1 and Y2 receptors while the C-terminal NPY fragments NPY18–36 and N-acetyl[Leu28,31]pNPY24–36 act only through the Y2 receptor. We have investigated the effects of intracerebroventricular (i.c.v.) administration of NPY1–36, NPY18–36 and N-acetyl[leu28,31]pNPY24–36 on LH secretion in the ovariectomised (OVX) ewe. These peptides were administered into a lateral ventricle (LV) or the third ventricle (3V) of OVX ewes during the non-breeding and breeding seasons. Microinjections of NPY were also made into the preoptic area (POA) during both seasons to investigate the effects of NPY at the level of the GnRH cell bodies. Tamed sheep were fitted with 19 gauge guide tubes into the LV, 3V or the septo-preoptic area (POA). Jugular venous blood samples were taken every 10 min for 3 h. Sheep were then given NPY1–36 (10 μg), NPY18–36 (100 μg) or saline vehicle into the LV; N-acetyl[Leu28,31]pNPY24–36 (100 μg), NPY1–36 (10 μg or 100 μg), NPY18–36 (10 μg or 100 μg) or saline vehicle into the 3V, or NPY1–36 (1 μg, 5 μg, 10 μg) into the POA. Blood sampling continued for a further 3 h. LH was measured in plasma by radioimmunoassay. LV or 3V injection of 10 μg NPY1–36 caused a small but significant (P<0·025) increase in the interval from the last pre-injection pulse of LH to the first post-injection LH pulse during the breeding season. Other LH pulse parameters were not significantly affected. NPY18–36 did not produce any significant change in LH pulsatility when injected into the LV, and neither peptide had any effect on plasma prolactin or GH levels. There was a significant (P<0·01) reduction in LH pulse frequency after 3V injection of 10 μg and 100 μg NPY and 100 μg NPY18–36. Pulse amplitude was reduced by 3V administration of the Y2 agonist, N-acetyl[Leu28–31]pNPY24–36 and 100 μ NPY18–36. When the amplitude of the first post-injection LH pulse was analysed, 10 μg NPY also had a significant (P<0·05) suppressive effect. During the non-breeding season, 100 μg NPY1–36 (but not 10 μg) decreased (P<0·01) LH pulse frequency. LH pulse amplitude was significantly (P<0·01) decreased by 100 μg NPY18–36. Doses of 10 μg NPY1–36 and 100 μg NPY18–36 had greater inhibitory effects on pulse frequency during the breeding season but the suppressive effect of 100 μg NPY was similar between seasons. Microinjections of NPY into the POA decreased (P<0·01) average plasma LH levels during the non-breeding season at a dose of 10 μg but did not significantly affect pulse frequency or amplitude. We conclude that a substantial component of the inhibitory action of NPY on LH secretion in the absence of steroids is mediated by the Y2 receptor. This inhibition is probably exerted by way of a presynaptic action on GnRH terminals in the median eminence as NPY does not modulate the frequency or amplitude of LH pulses at the level of the GnRH cell bodies in the POA. Journal of Endocrinology (1995) 147, 565–579


2014 ◽  
Vol 99 (8) ◽  
pp. 2887-2896 ◽  
Author(s):  
Jessicah S. Collins ◽  
Jennifer P. Beller ◽  
Christine Burt Solorzano ◽  
James T. Patrie ◽  
R. Jeffrey Chang ◽  
...  

Context: Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown. Objective: The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia. Design: This was a cross-sectional analysis. Setting: The study was conducted at a clinical research center. Patients or Other Participants: Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study. Intervention: Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am. Main Outcome Measure: Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep). Results: Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively). Conclusions: Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.


Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3717-3724
Author(s):  
M. Shahab ◽  
M. Vargas Trujillo ◽  
T. M. Plant

A somatic signal has been posited to trigger the pubertal resurgence in pulsatile GnRH secretion that initiates puberty in highly evolved primates. That GH might provide such a signal emerged in 2000 as a result of a study reporting that circulating nocturnal GH concentrations in castrated juvenile male monkeys increased in a 3-week period immediately preceding the pubertal resurgence of LH secretion. The present study was conducted to reexamine this intriguing relationship, again in an agonadal model. Four castrated juvenile male monkeys were implanted with indwelling jugular catheters, housed in remote sampling cages, and subjected to 24 hours of sequential blood sampling (every 30 min) every 2 weeks from 19.5 to 22 months of age. Twenty-four-hour profiles of circulating GH concentrations were analyzed using the pulse detection algorithm, PULSAR, and developmental changes in pulsatile GH release with respect to the initiation of the pubertal rise of LH secretion (week 0; observed between 22.5 and 32 mo of age) were examined for significance by a repeated-measures ANOVA. Changes in the parameters of pulsatile GH secretion, including mean 24-hour GH concentration and GH pulse frequency and pulse amplitude for 3 (n = 4) and 6 (n = 3) months before week 0 were unremarkable and nonsignificant. These findings fail to confirm those of the earlier study and lead us to conclude that the timing of the pubertal resurgence of GnRH release in the male monkey is not dictated by GH. Reasons for the discrepancy between the two studies are unclear.


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