Radiotelemetric Monitoring of Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity Throughout the Menstrual Cycle of the Rhesus Monkey<sup>*</sup>

O’Byrne, Kevin; Thalabard, Jean-Christophe; Grosser, Peter M.; Wilson, Richard C.; Williams, Christopher S.; Chen, M.-D.; Ladendorf, D.; Hotchkiss, J.; Knobil, E.

doi:10.1210/endo-129-3-1207

Cited by 124 publications

(75 citation statements)

References 50 publications

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“…Previous studies on electrical activity in the hypothalamus during the surge, using radiotelemetric recordings of GnRH pulse generator activity, indicated a decrease in multiple unit activity (MUA) associated with LH surges in monkeys and goats (52,53). This finding contrasts with the present data, which show dramatic increases in GnRH neuron activity associated with the LH surge in mice.…”

Section: Discussioncontrasting

confidence: 99%

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Christian

Mobley

Moenter

2005

Proc. Natl. Acad. Sci. U.S.A.

192

213

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A robust gonadotropin-releasing hormone (GnRH) surge is a prerequisite signal for the luteinizing hormone (LH) surge that triggers ovulation. In rodents, the GnRH surge is initiated by elevated estradiol and a diurnal switch in estrogen action from negative to positive feedback. The ability of constant estradiol treatment to induce daily LH surges was tested in adult mice that were ovariectomized (OVX) or OVX and treated with estradiol implants (OVX؉E). LH in OVX mice showed no time-of-day difference. In contrast, OVX؉E mice showed a large LH surge (8-to 124-fold relative to the a.m.) in p.m. samples on d 2-5 post-OVX؉E. Targeted extracellular recordings were used to examine changes in firing activity of GnRH neurons in brain slices. There was no time-of-day difference in cells from OVX mice. In contrast, OVX؉E cells recorded in the p.m. showed an increased mean firing rate and instantaneous firing frequency, which could increase GnRH release, and decreased duration of quiescence between bouts of firing, possibly reflecting increased pulse frequency, compared with cells recorded in the a.m. In the a.m., OVX؉E cells showed changes in GnRH neuron firing reflecting negative feedback compared with OVX cells, whereas in the p.m., OVX؉E cells exhibited changes suggesting positive feedback. These data indicate that differences in pattern and level of individual GnRH neuron firing may reflect the switch in estradiol action and underlie GnRH surge generation. The persistence of altered GnRH neuron activity in slices indicates that this approach can be used to study the neurobiological mechanisms of surge generation.luteinizing hormone ͉ mouse model ͉ surge ͉ electrophysiology ͉ neuroendocrinology

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Section: Discussioncontrasting

confidence: 99%

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Christian

Mobley

Moenter

2005

Proc. Natl. Acad. Sci. U.S.A.

192

213

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“…Experimental inferences concerning the unique physiological transition that terminates the LF and introduces the luteal phase differ. For example, radiotelemetric monitoring of mediobasal hypothalamic multiunit electrical-bursting activity (a putative physiological correlate of GnRH pulses) suggests that discrete GnRH event frequency decreases or does not change during the preovulatory LH surge in the monkey and rat (22,23). Other analyses based on systemic estimates of LH pulsatility and central monitoring of hypothalamo-pituitary portal-venous and cerebrospinal fluid GnRH pulsatility report amplification of GnRH pulse amplitude and variable acceleration of GnRH secretory-burst frequency during the ascending limb of the LH surge in the rat, monkey, and sheep (8,21,31,36,49).…”

Section: Discussionmentioning

confidence: 99%

Control of LH secretory-burst frequency and interpulse-interval regularity in women

Keenan¹,

Evans²,

Veldhuis³

2003

American Journal of Physiology-Endocrinology and Metabolism

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. Control of LH secretory-burst frequency and interpulse-interval regularity in women. Am J Physiol Endocrinol Metab 285: E938-E948, 2003; 10.1152/ajpendo.00133. 2003.-Hypothalamic neurons generate discrete bursts of gonadotropin-releasing hormone (GnRH) and thereby pulses of luteinizing hormone (LH) at randomly timed intervals centered on a probabilistic mean frequency. We tested the hypothesis that physiological mechanisms govern not only the number but also the stochastic dispersion of the GnRH/LH pulse-renewal process in humans; for example, in young women in the early (EF) and late (LF) follicular and midluteal (ML) phases of the menstrual cycle (n ϭ 18) and in postmenopausal individuals (PM, n ϭ 16). To this end, we quantify stochastic interpulse variability by way of the orderindependent, two-parameter Weibull renewal process (Keenan DM and Veldhuis J. Am J Physiol Regul Integr Comp Physiol 281: R1917-R1924, 2001) and the sequence-specific, modelfree approximate-entropy statistic (ApEn) (Pincus SM. Proc Natl Acad Sci USA 88: 2297-2301, 1991. Statistical testing unveiled 1) reduced probabilistic mean LH secretory-burst frequency (lower of the Weibull distribution) in ML compared with each of EF, LF, and PM (P Ͻ 0.001); 2) quantifiably more regular LH interburst-interval sets (elevated ␥ of the Weibull density) in PM than in each of EF, LF, and ML (P Ͻ 0.01); 3) uniquely prolonged latency to maximal LH secretion within individual secretory bursts in ML (P Ͻ 0.01); and 4) comparably mean random, sequential LH interburstinterval and mass values (normalized ApEn) among the distinct hormonal milieus. From these data, we postulate that sex steroids and age determine daily LH secretory-burst number, quantifiable pulse-renewal variability, and secretory-waveform evolution.age; reproduction; human; female; pituitary; hypothalamus; leuteinizing hormone DIRECT APPRAISAL of hypothalamic gonadotropin-releasing hormone (GnRH) pulse-generator activity is not feasible in humans. However, the timing of discrete luteinizing hormone (LH) pulses in the peripheral circulation provides a surrogate marker of GnRH release in the setting of normal gonadotrope responsivity. The basis for this inference includes the strong concordance between episodic GnRH and LH release in the rodent, lagamorph, ruminant, and primate (3,18,20,27,31,36,49), the consistent correspondence between arcuate nucleus electrophysiological correlates of GnRH outflow and individual pulses of LH in jugular venous blood in the monkey and rat (9, 46), and the rapid suppressibility of peripheral LH pulses by immunoneutralization of GnRH or pharmacological blockade of GnRH reception (35,37).Synchronous GnRH neuronal firing and attendant LH secretory bursts recur at random intervals with no serial correlation of successive waiting times (1, 2, 12, 13). We recently highlighted the utility of quantifying the stochastic properties of the pulse-renewal process by the two-parameter Weibull probability distribution (10, 11). Unlike the derivative (1-parameter) Poisson...

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“…It has been demonstrated that electrophysiological manifestations of the GnRH pulse generator are represented as characteristic increases in MUA (MUA volleys) that are exclusively associated with LH pulses in the monkey [8], rat [9] and goat [10,11]. It might be that observed MUA volleys reflect the pulsatile activation of GnRH nerve terminals as they traverse en passant to the ME.…”

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confidence: 99%

Effects of Brief Exposure of Male Pheromone on Multiple-Unit Activity at Close Proximity to Kisspeptin Neurons in the Goat Arcuate Nucleus

Murata

Wakabayashi

Sakamoto

et al. 2011

Journal of Reproduction and Development

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Abstract. Exposure of females to the male pheromone induces pulsatile release of gonadotropin-releasing hormone (GnRH) in goats. Recently, kisspeptin neurons in the arcuate nucleus (ARC) have been suggested to represent the proximate source of the GnRH pulse generator. In this study, we examined the effects of the pheromone on multipleunit activity (MUA) in female goats fitted with recording electrodes aimed at the ARC kisspeptin neurons. In all eight goats, periodic bursts in MUA (MUA volleys), which were considered to be electrophysiological manifestations of the GnRH pulse generator, were observed. The mean intervolley interval (T) during the control period was calculated in each goat that was then exposed to the male pheromone for 1 sec at timings of 1/4 T, 1/2 T or 3/4 T after one regularly occurring MUA volley. An instantaneous rise in MUA was observed immediately after the exposure regardless of timing. Exposure at a timing of 3/4 T resulted in an MUA volley within 60 sec following the instantaneous rise in all goats. In contrast, an MUA volley was induced in only 2 goats by exposure at 1/2 T, while exposure at 1/4 T failed to induce an MUA volley in any goats. These results suggest that transmission of the pheromone signal to the ARC, represented by an instantaneous rise, activates the GnRH pulse generator. Moreover, the timing-dependent pheromone action in inducing an MUA volley indicates that the GnRH pulse generator has a refractory period for the pheromone signal after the burst. Key words: GnRH pulse generator, Goat, Kisspeptin, Male effect, Pheromone (J. Reprod. Dev. 57 : 197-202, 2011) n goats and sheep, exposure of seasonally anestrous females to the primer pheromone secreted by sexually mature males results in an out-of-seasonal ovulation [1][2][3][4]. Since the initial endocrine event following reception of the pheromone is the stimulation of pulsatile luteinizing hormone (LH) secretion, it has been thought that the central target of the pheromone signal is the GnRH pulse generator [1,[3][4][5], i.e., the neural substrate that generates intermittent GnRH discharges into the portal vessels, thereby regulating pulsatile LH secretion into the peripheral circulation [6,7].Although the neural identity of the GnRH pulse generator per se was unclear, it was possible to measure its activity by recording multiple-unit activity (MUA) at the mediobasal hypothalamus. It has been demonstrated that electrophysiological manifestations of the GnRH pulse generator are represented as characteristic increases in MUA (MUA volleys) that are exclusively associated with LH pulses in the monkey [8], rat [9] and goat [10,11]. It might be that observed MUA volleys reflect the pulsatile activation of GnRH nerve terminals as they traverse en passant to the ME. Using this technique, Hamada et al. [12] showed that exposure of the female goat to male hair used as a pheromone source promptly induced an MUA volley, demonstrating for the first time that the pheromone action is in fact intimately associated with the GnRH pul...

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Radiotelemetric Monitoring of Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity Throughout the Menstrual Cycle of the Rhesus Monkey^*

Cited by 124 publications

References 50 publications

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Control of LH secretory-burst frequency and interpulse-interval regularity in women

Effects of Brief Exposure of Male Pheromone on Multiple-Unit Activity at Close Proximity to Kisspeptin Neurons in the Goat Arcuate Nucleus

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Radiotelemetric Monitoring of Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity Throughout the Menstrual Cycle of the Rhesus Monkey*

Cited by 124 publications

References 50 publications

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Control of LH secretory-burst frequency and interpulse-interval regularity in women

Effects of Brief Exposure of Male Pheromone on Multiple-Unit Activity at Close Proximity to Kisspeptin Neurons in the Goat Arcuate Nucleus

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Product

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Radiotelemetric Monitoring of Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity Throughout the Menstrual Cycle of the Rhesus Monkey^*