Evidence of gonadal steroid-independent changes in activity of the central LH-releasing hormone pulse generator in developing bull calves

1986 ◽  
Vol 111 (1) ◽  
pp. 67-73 ◽  
Author(s):  
M. J. D'Occhio ◽  
D. R. Gifford ◽  
T. Weatherly ◽  
B. P. Setchell
Keyword(s):  
Pulse Generator ◽  
Age Groups ◽  
Pulse Frequency ◽  
Releasing Hormone ◽  
Age Related ◽  
Bull Calves ◽  
Serum Lh ◽  
Transient Rise ◽  
Lh Releasing Hormone ◽  
Lh Secretion

ABSTRACT To ascertain whether temporal changes in activity of the hypothalamo-pituitary axis in prepubertal bulls may occur independently of shifts in sensitivity to steroid feedback, the acute post-castration rise in serum gonadotrophins was monitored in bull calves castrated at monthly intervals from 4 to 9 months of age. Since a major feature of the gonadotrophin profiles of developing bulls is a change in LH pulse frequency early in life, pulsatile LH secretion after castration was used as an index of activity of the central LH-releasing hormone (LHRH) pulse generator. Relative to the day of castration (day 0) bull calves (n = 4) were bled at 20-min intervals for 8 h on day −3 and at 10-min intervals for 4 h on days 3, 5 and 7. During the first week after castration, 4-month-old bulls showed a higher (P<0·05) frequency of LH pulses compared with bulls at 8 and 9 months (1·13, 0·88 and 0·75 pulses/h respectively; pooled s.e.m.= 0·13). Mean LH levels before castration were higher (P<0·05) in 4-month-old bulls than in bulls at 7, 8 and 9 months (0·92, 0·37, 0·31, 0·38 μg/l respectively; pooled s.e.m. = 0·12). After castration mean LH levels did not differ with age. Mean FSH levels did not differ among age groups either before or after castration. Increased serum LH levels in 4-month-old bulls confirmed the transient rise in LH secretion that occurs at this time in developing bull calves. Age-related differences in LH pulse frequency observed after castration suggested that in prepubertal bulls changes in activity of the central LHRH pulse generator can occur independently of steroid feedback mechanisms. J. Endocr. (1986) 111, 67–73

scholarly journals Effects of treatment with LH releasing hormone before the early increase in LH secretion on endocrine and reproductive development in bull calves

Reproduction ◽  
1997 ◽  
Vol 111 (1) ◽  
pp. 41-50 ◽  
Author(s):  
R. K. Chandolia ◽  
A. Honaramooz ◽  
P. M. Bartlewski ◽  
A. P. Beard ◽  
N. C. Rawlings
Keyword(s):  
Reproductive Development ◽  
Releasing Hormone ◽  
Bull Calves ◽  
Early Increase ◽  
Lh Releasing Hormone ◽  
Lh Secretion

Suppression of LH secretion by oestradiol, dihydrotestosterone and trenbolone acetate in the acutely castrated bull

1984 ◽  
Vol 100 (1) ◽  
pp. 107-112 ◽  
Author(s):  
T. W. Gettys ◽  
M. J. D'Occhio ◽  
D. M. Henricks ◽  
B. D. Schanbacher
Keyword(s):  
Feedback Control ◽  
Pituitary Gland ◽  
Treated Group ◽  
Primary Site ◽  
Trenbolone Acetate ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Lh Releasing Hormone ◽  
Lh Secretion

ABSTRACT Twenty acutely castrated bulls were used to investigate the role of androgenic and oestrogenic steroids in the feedback control of LH secretion. The effects of 5α-dihydrotestosterone (DHT) or the growth stimulants trenbolone acetate (TBA) or oestradiol-17β (OE2) on serum LH secretory profiles were measured. In addition, pituitary LH responses to exogenous LH releasing hormone (LHRH) were determined to differentiate between hypothalamic and pituitary sites of steroid action. At the time of castration, two groups of animals were given implants of either 45 mg OE2 or 200 mg TBA. Another group received equivalent to 30 mg daily injections of DHT. Control steers showed an increase in LH from 2·4 ± 0·5 (s.e.m.) μg/l to 7·0 ± 0·5 μg/l during the week after castration. Treatment with DHT and TBA prevented the post-castration rise in serum LH. In contrast, steers given implants of OE2 showed a significantly greater increase in LH than controls 1 day after castration, but by day 5 LH declined in the OE2-treated group to precastration values. Five weeks after castration control steers secreted LH in pulses at intervals of 40–50 min and with an amplitude of 4·2± 0·4 μg/l. Pulses were not detected in the LH profiles of the steroid-treated steers. Dihydrotestosterone and TBA significantly reduced pituitary LH responses to exogenous LHRH, whereas steers receiving OE2 showed LH responses to LHRH which were similar to those observed in castrated controls. These results support the hypothesis that androgenic and oestrogenic components participate separately in the feedback control of LH secretion in the bull. A similar LH response to exogenous LHRH in control and OE2-treated animals suggests that the primary site of oestrogen feedback is at the level of the hypothalamus. Conversely, the small LH response to LHRH in androgen-treated animals suggests that androgen feedback is, in part, imposed at the level of the pituitary gland. Interestingly, LH secretion is regulated by dosages of androgenic and oestrogenic steroids which are available commercially as growth stimulants for cattle. J. Endocr. (1984) 100, 107–112

Gonadotrophin secretion in prepubertal bull calves born in spring and autumn

Reproduction ◽  
2000 ◽  
pp. 159-167 ◽  
Author(s):  
JP Aravindakshan ◽  
A Honaramooz ◽  
PM Bartlewski ◽  
AP Beard ◽  
RR Pierson ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Scrotal Circumference ◽  
Bull Calves ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Age At Puberty ◽  
Lh Secretion ◽  
Vital Factor

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.

Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women

1996 ◽  
Vol 135 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Joaquin Lado-Abeal ◽  
Jose L Liz ◽  
Carlos Rey ◽  
Manuel Febrero ◽  
Jose Cabezas-Cerrato
Keyword(s):  
Luteinizing Hormone ◽  
Sodium Valproate ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Gabaergic System ◽  
Luteinizing Hormone Secretion ◽  
Serum Lh ◽  
Nutrition Service ◽  
Significant Difference ◽  
Lh Secretion

Lado-Abeal J, Liz JL, Rey C, Febrero M, Cabezas-Cerrato J. Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women. Eur J Endocrinol 1996;135:293–8. ISSN 0804–4643 It is well established that valproate increases hypothalamic concentrations of γ-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second, 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' nonparametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator. J Cabezas-Cerrato, Endocrinology and Nutrition Service, General Hospital of Galicia, c/Galeras s/n 15705, Santiago de Compostela, La Coruña, Spain

Pulsatile LH secretion in streptozotocin-induced diabetes in the rat

1991 ◽  
Vol 131 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Q. Dong ◽  
R. M. Lazarus ◽  
L. S. Wong ◽  
M. Vellios ◽  
D. J. Handelsman
Keyword(s):  
Weight Loss ◽  
Insulin Treatment ◽  
Pulse Generator ◽  
Latin Square ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Metabolic Effect ◽  
Male Rat ◽  
Free Access ◽  
Lh Secretion

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

scholarly journals Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men

2010 ◽  
Vol 299 (4) ◽  
pp. E675-E682 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Paul Y. Takahashi ◽  
Daniel M. Keenan ◽  
Peter Y. Liu ◽  
Kristi L. Mielke ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Negative Feedback ◽  
Pulse Frequency ◽  
Analysis Of Covariance ◽  
Double Blind ◽  
Healthy Men ◽  
Age Related ◽  
Lh Release ◽  
Lh Secretion ◽  
Double Blind Crossover Study

Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20–73 yr, BMI 21–32 kg/m2, participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion ( P = 0.003), 2) potentiated the age-related abbreviation of LH secretory bursts ( P = 0.025), 3) suppressed incremental GnRH-induced LH release ( P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release ( P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH ( P = 0.002) and T ( P = 0.017) concentrations, 2) accelerating LH pulse frequency ( P = 0.013), 3) amplifying total (basal plus pulsatile) LH ( P = 0.002) and T ( P < 0.001) secretion, 4) shortening LH secretory bursts ( P = 0.032), and 5) reducing LH secretory regularity ( P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion ( P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men.

Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect

1993 ◽  
Vol 128 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Lise Duranteau ◽  
Philippe Chanson ◽  
Joelle Blumberg-Tick ◽  
Guy Thomas ◽  
Sylvie Brailly ◽  
...  
Keyword(s):  
Single Pulse ◽  
Serum Testosterone ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Gonadotropin Secretion ◽  
Pulsatile Gnrh ◽  
Serum Lh ◽  
Before And After ◽  
Gnrh Therapy ◽  
Lh Secretion

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.

scholarly journals Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison
Keyword(s):  
Luteinizing Hormone ◽  
High Frequency ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Male Mice ◽  
Intact Male ◽  
Luteinizing Hormone Secretion ◽  
Pulse Profile ◽  
Lh Secretion

Abstract The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.

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
Keyword(s):  
Sexual Maturity ◽  
Initial Step ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Serum Samples ◽  
Bull Calf ◽  
Bull Calves ◽  
Early Increase ◽  
Early Rise ◽  
Lh Secretion

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

scholarly journals Suppression of the GnRH Pulse Generator by Neurokinin B Involves a κ-Opioid Receptor-Dependent Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4894-4904 ◽  
Author(s):  
P. Grachev ◽  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. L. di Domenico ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Neurokinin B ◽  
Kndy Neurons ◽  
Lh Secretion ◽  
Dose Dependent

Abstract Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17β-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.

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