Sleep deprivation reduces LH secretion in men independently of melatonin

Abstract. Melatonin affects gonadal function in nonprimate mammals. Confirmatory data in man are not available. We assessed melatonin's acute effects on luteinizing hormone secretion in 17 normal men. We studied these men in conditions of sleep in the dark, and sleep deprivation in bright light, dim light, and bright light combined with a physiologically relevant infusion of melatonin, while measuring blood levels of immunoreactive LH every 20 min for 7 h. We compared overnight LH secretion, and LH pulse frequency, amplitude, length, interval and area under the curve using a modification of the PULSAR peak identification program, among the four treatments. Areas under the curve for peaks in all three conditions of sleep deprivation were lower than in normal sleep. The presence or absence of melatonin had no additional effect. We conclude that acute suppression of melatonin does not affect LH pulse parameters in normal man, but that sleep deprivation may reduce the amount of LH secreted per pulse.

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Clobazam increases pulsatile luteinizing hormone secretion in normal men

Acta Endocrinologica ◽

10.1530/acta.0.1200485 ◽

1989 ◽

Vol 120 (4) ◽

pp. 485-489 ◽

Cited By ~ 3

Author(s):

G. Thomas ◽

J. C. Thalabard ◽

M. Duet ◽

C. Girre ◽

P. E. Fournier

Keyword(s):

Luteinizing Hormone ◽

Oral Administration ◽

Hormone Secretion ◽

Pulse Frequency ◽

Healthy Male ◽

Luteinizing Hormone Secretion ◽

Gnrh Release ◽

Normal Men ◽

Lh Secretion ◽

Hypothalamic Level

Abstract. To investigate the effects of the 1,5-benzodiazepine, clobazam, on LH secretion in normal men, LH pulsatile secretion was defined after oral administration of 40 mg of clobazam or a placebo to 6 healthy male volunteers, according to a randomized cross-over design. LH pulse frequency increased significantly from a mean of 3.8 (range 3–5 pulses/8 h after placebo, to a mean of 5 (range 4–7) pulses/8 h (P< 0.05), after clobazam. Mean LH concentrations and peak amplitudes did not change significantly. These results suggest that clobazam mediates its effects on LH secretion at the hypothalamic level by increasing the frequency of episodic GnRH release.

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Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽

10.1210/endocr/bqz045 ◽

2020 ◽

Vol 161 (2) ◽

Cited By ~ 4

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.

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Estradiol Enables Chronic Corticosterone to Inhibit Pulsatile Luteinizing Hormone Secretion and Suppress Kiss1 Neuronal Activation in Female Mice

Neuroendocrinology ◽

10.1159/000502978 ◽

2019 ◽

Vol 110 (6) ◽

pp. 501-516 ◽

Cited By ~ 6

Author(s):

Michael J. Kreisman ◽

Richard B. McCosh ◽

Katherine Tian ◽

Christopher I. Song ◽

Kellie M. Breen

Keyword(s):

Luteinizing Hormone ◽

Hormone Secretion ◽

Pulse Frequency ◽

Dependent Manner ◽

Neuronal Activation ◽

Luteinizing Hormone Secretion ◽

Female Mice ◽

Enhanced Sensitivity ◽

Ovarian Cyclicity ◽

Lh Secretion

Introduction: Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have previously shown that a chronic stress level of corticosterone can impair ovarian cyclicity in intact mice by preventing follicular-phase endocrine events. Objective: This study is aimed at investigating if corticosterone can disrupt LH pulses and whether estradiol is necessary for this inhibition. Methods: Our approach was to measure LH pulses prior to and following the administration of chronic corticosterone or cholesterol in ovariectomized (OVX) mice treated with or without estradiol, as well as assess changes in arcuate kisspeptin (Kiss1) neuronal activation, as determined by co-expression with c-Fos. Results: In OVX mice, a chronic 48 h elevation in corticosterone did not alter the pulsatile pattern of LH. In contrast, corticosterone induced a robust suppression of pulsatile LH secretion in mice treated with estradiol. This suppression represented a decrease in pulse frequency without a change in amplitude. We show that the majority of arcuate Kiss1 neurons contain glucocorticoid receptor, revealing a potential site of corticosterone action. Although arcuate Kiss1 and Tac2 gene expression did not change in response to corticosterone, arcuate Kiss1 neuronal activation was significantly reduced by chronic corticosterone, but only in mice treated with estradiol. Conclusions: Collectively, these data demonstrate that chronic corticosterone inhibits LH pulse frequency and reduces Kiss1 neuronal activation in female mice, both in an estradiol-dependent manner. Our findings support the possibility that enhanced sensitivity to glucocorticoids, due to ovarian steroid milieu, may contribute to reproductive impairment associated with stress or pathophysiologic conditions of elevated glucocorticoids.

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Control of luteinizing hormone secretion in ewes by endogenous opioids and the dopaminergic system during short seasonal anoestrus: rôle of plane of nutrition

Animal Science ◽

10.1017/s1357729800016520 ◽

1997 ◽

Vol 65 (2) ◽

pp. 217-224 ◽

Cited By ~ 10

Author(s):

F. Forcada ◽

J. M. Lozano ◽

J. A. Abecia ◽

L. Zarazaga

Keyword(s):

Luteinizing Hormone ◽

Receptor Antagonist ◽

Dopaminergic System ◽

Hormone Secretion ◽

Pulse Frequency ◽

Endogenous Opioids ◽

Endogenous Opioid ◽

Luteinizing Hormone Secretion ◽

Lh Secretion

AbstractThe role of endogenous opioids and the dopaminergic system on the inhibition of luteinizing hormone (LH) secretion during early and late anoestrus, together with its modulation by the plane of nutrition were investigated in ewes with a short anoestrous season. In early anoestrus (22 March; day 0), two groups of ovariectomized, oestradiol-treated adult Rasa Aragonesa ewes, maintained under natural photoperiod at 41°N, were given enough food to provide 1·4 × (high; H; no. = 6) or 0·5 × (low; L; no. = 6) energy requirements for maintenance. The effects of administration of the opiate receptor antagonist naloxone (1 mg/kg at four 1-h intervals) (day 15) and of the dopaminergic2 receptor antagonist pimozide (0·08 mg/kg) (day 21) on LH secretion were assessed. A second experiment was carried out in late anoestrus (21 June) using the same protocol. A significant increase in LH pulse frequency after naloxone treatment for both H and L groups was detected in late anoestrus. Number ofLH pulses after naloxone injections in early anoestrus also increased in H (P < 0·05) and L ewes (P = 0·08). The effect of pimozide injection on mean LH pulse frequency was greater in early than in late anoestrus, especially in ewes receiving a high plane of nutrition (P < 0·05 and P = 0·07 for H and L ewes, respectively in April and P = 0·07 for H ewes in July). A significant increase of LH pulse amplitude was also detected in early anoestrus in H ewes (P < 0·01). These results provide evidence that endogenous opioid mechanisms are involved in the inhibition ofLH pulsatile release both in early and late anoestrus in ewes with a short seasonal anoestrus. The ability of pimozide to increase LH pulse frequency in early anoestrus could be enhanced by a high plane of nutrition in the breed studied.

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Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pituitary Level?

Endocrinology ◽

10.1210/en.2003-1114 ◽

2004 ◽

Vol 145 (2) ◽

pp. 692-698 ◽

Cited By ~ 84

Author(s):

Kellie M. Breen ◽

Fred J. Karsch

Keyword(s):

Plasma Cortisol ◽

Hormone Secretion ◽

Pulse Amplitude ◽

Pulse Frequency ◽

Luteinizing Hormone Secretion ◽

Inflammatory Stress ◽

Gnrh Secretion ◽

Gnrh Release ◽

Acute Increase ◽

Lh Secretion

Abstract Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we conducted two experiments in ovariectomized ewes to determine whether an acute increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH release into pituitary portal blood or by inhibiting pituitary responsiveness to GnRH. First, we sampled pituitary portal and peripheral blood after administration of cortisol to mimic the elevation stimulated by an immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH pulse frequency, however, was unaffected. In contrast, cortisol did not suppress either parameter of GnRH secretion. Next, we assessed the effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration, and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH release.

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279. A dynamic model of the control of pulsatile luteinizing hormone secretion by gonadotrophin-releasing hormone

Reproduction Fertility and Development ◽

10.1071/srb05abs279 ◽

2005 ◽

Vol 17 (9) ◽

pp. 116

Author(s):

T. R. Ferasyi ◽

H. Barrett ◽

D. Blache ◽

G. B. Martin

Keyword(s):

Slow Rate ◽

Membrane Surface ◽

Hormone Secretion ◽

Pulse Frequency ◽

Recycling Rate ◽

Luteinizing Hormone Secretion ◽

Critical Control Points ◽

High Pulse Frequency ◽

Lh Secretion ◽

Very High

Infusion of GnRH in a continuous manner or with a very high pulse frequency initially stimulates but then downregulates LH secretion.1,2 This phenomenon is caused by the slow rate of internalisation of the GnRH receptor (GnRH-R) and the subsequent slow return of receptors to the plasma membrane of the gonadotroph.3 Pulsatile release of GnRH overcomes this problem by allowing a delay between successive stimulations. It is difficult to determine the relative importance of critical control points in this process in an animal model because GnRH activity reflects integrated inputs from many internal and external factors. We are therefore using SAAM II software to develop a compartmental model of the relationship between GnRH-R availability and LH responses following changes in GnRH pulse frequency. The model has three receptor states (free, bound, and internalised) and one LH compartment (Fig. 1). We assumed LH release is a function of the amount of receptor that binds GnRH. Following GnRH binding, receptors are rapidly lost as they enter the internalised state and then slowly returned to the membrane surface. We further assumed that the slow rate of receptor return explains the decrease in LH response with very high frequencies of GnRH pulses. The values for parameters were based on data obtained from experiments with sheep. In our current version of the model, downregulation is observed when gonadotrophs are stimulated with GnRH pulses every 15 min (Fig. 1), but not with pulses every 30 or 60 min, at a slow recycling rate (0.004 min–1). In contrast, LH secretion increases when GnRH is pulsed every 15 min and recycling rate is increased to 0.04 min–1. This suggests that, in sheep, a recycling rate between 0.004 and 0.04 min–1 is a critical aspect of the intracellular control of the process. Future work will include steroid feedback loops.

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Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep

Acta Endocrinologica ◽

10.1530/acta.0.1020499 ◽

1983 ◽

Vol 102 (4) ◽

pp. 499-504 ◽

Cited By ~ 15

Author(s):

M. J. D'Occhio ◽

B. D. Schanbacher ◽

J. E. Kinder

Keyword(s):

Luteinizing Hormone ◽

Pulse Generator ◽

Hormone Secretion ◽

Pulse Interval ◽

Serum Concentrations ◽

Luteinizing Hormone Secretion ◽

Lh Release ◽

Lh Secretion ◽

Additional Feedback ◽

Male Sheep

Abstract. The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

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Changes in the characteristics of pulsatile luteinizing hormone secretion during the oestrous cycle and after ovariectomy and oestrogen treatment in female rats

Journal of Endocrinology ◽

10.1677/joe.0.0940177 ◽

1982 ◽

Vol 94 (2) ◽

pp. 177-182 ◽

Cited By ~ 16

Author(s):

Takashi Higuchi ◽

Masazumi Kawakami

Keyword(s):

Hormone Secretion ◽

Pulse Amplitude ◽

Pulse Frequency ◽

Oestrous Cycle ◽

Female Rats ◽

Ovariectomized Rats ◽

Luteinizing Hormone Secretion ◽

Oestrogen Treatment ◽

Serum Lh ◽

Lh Release

Changes in the characteristics of LH secretory pulses in female rats were determined in different hormonal conditions; during the oestrous cycle and after ovariectomy and oestrogen treatment. The frequency and amplitude of the LH pulses were stable during the oestrous cycle except at oestrus when a pattern could not be discerned because of low LH concentrations. These were significantly lower than those measured during other stages of the cycle. Mean LH concentrations and LH pulse amplitudes increased with time up to 30 days after ovariectomy. The frequency of the LH pulse was unchanged 4 days after ovariectomy when mean LH levels had already increased. The frequency increased 10 days after ovariectomy and then remained stable in spite of a further increase in mean serum LH concentrations. Oestradiol-17β injected into ovariectomized rats caused a decrease in LH pulse amplitude but no change in pulse frequency. One day after treatment with oestradiol benzoate no LH pulse was detectable, probably because the amplitude was too small. A generator of pulsatile LH release is postulated and an oestrogen effect on its function is discussed.

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

Acta Endocrinologica ◽

10.1530/eje.0.1350293 ◽

1996 ◽

Vol 135 (3) ◽

pp. 293-298 ◽

Cited By ~ 2

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

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