Generation of the GnRH Surge and LH Surge by the Positive Feedback Effect of Estrogen

Clarke, Iain J.

doi:10.1002/9781119233275.ch13

Cited by 6 publications

(5 citation statements)

References 79 publications

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“…On the other hand, the surge-mode of GnRH secretion induces a luteinizing hormone (LH) surge [11, 12], which is found in the preovulatory stage of the estrous cycle and evokes ovulation and corpus luteum formation. It is apparent that the surge-mode of GnRH secretion is induced by the positive feedback action of high levels of estrogen secreted by mature follicles [15]. During the last three decades of the 20th century, intensive studies were performed to address the involvement of various neurotransmitters and neuropeptides in the regulation of two modes of GnRH/gonadotropin secretion; however the mechanisms controlling GnRH/gonadotropin secretion were not fully elucidated until the discovery of kisspeptin at the beginning of the 21st century.…”

Section: Introductionmentioning

confidence: 99%

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

Uenoyama

Inoue

Maeda

et al. 2018

Journal of Reproduction and Development

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Kisspeptin, identified as a natural ligand of GPR54 in 2001, is now considered as a master regulator of puberty and subsequent reproductive functions in mammals. Our previous studies using Kiss1 knockout (KO) rats clearly demonstrated the indispensable role of kisspeptin in gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. In addition, behavioral analyses of Kiss1 KO rats revealed an organizational effect of kisspeptin on neural circuits controlling sexual behaviors. Our studies using transgenic mice carrying a region-specific Kiss1 enhancer-driven reporter gene provided a clue as to the mechanism by which estrogen regulates Kiss1 expression in hypothalamic kisspeptin neurons. Analyses of Kiss1 expression and gonadotropin secretion during the pubertal transition shed light on the mechanism triggering GnRH/gonadotropin secretion at the onset of puberty in rats. Here, we summarize data obtained from the aforementioned studies and revisit the physiological roles of kisspeptin in the mechanism underlying reproductive functions in mammals.

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Section: Introductionmentioning

confidence: 99%

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

Uenoyama

Inoue

Maeda

et al. 2018

Journal of Reproduction and Development

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“…Alternately, it is possible that GLP-1 may act without affecting the mechanisms generating the GnRH/LH surge, e.g. on GnRH neuronal cell bodies or on pituitary gonadotropes ( Clarke 2018 , Herbison 2018 ). Nevertheless, exendin-4 treatment at or near the time of the LH surge may have had a modulatory effect, with a more protracted surge occurring in some treated ewes ( n = 2) ( Fig.…”

Section: Discussionmentioning

confidence: 99%

The GLP-1 agonist, exendin-4, stimulates LH secretion in female sheep

Simpson

Clarke

Scott

et al. 2023

Journal of Endocrinology

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Our previous studies showed that microinjection into the median eminence of the sheep of glucagon-like peptide- 1 (GLP-1) or its receptor agonist Exendin-4 stimulates luteinizing hormone (LH) secretion but it is unknown whether the same effect may be obtained by systemic administration of the same. The present study measured the response in terms of plasma LH concentrations, to intravenous (iv) infusion of Exendin-4. A preliminary study showed that infusion of 2mg Exendin-4 into ewes produced a greater LH response in the follicular phase of the oestrous cycle than the luteal phase. Accordingly, the main study monitored plasma LH levels in response to either 0.5mg or 2mg Exendin-4 or vehicle (normal saline) delivered by jugular infusion for 1h in the follicular phase of the oestrous cycle. Blood samples were collected at 10 min intervals before, during and after infusion. Both doses of Exendin-4 increased mean plasma LH concentrations and increased LH peripheral pulse amplitude. There was no effect on inter-pulse interval or timing of the preovulatory LH surge. These doses of Exendin-4 did not alter plasma insulin or glucose concentrations. Quantitative PCR of the gastrointestinal tract samples from a population of ewes confirmed expression of the preproglucagon gene (GCG). Expression increased aborally and was greatest in the rectum. It is concluded that endogenous GLP-1, most likely derived from the hind-gut may act systemically to stimulate LH secretion. The present data suggest that this effect may be obtained with levels of agonist that are lower than those functioning as an incretin.

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“…These rostrally located Kp neurons, along with GnRH neurons in the same region, display Fos labelling after the start of the GnRH surge (Hoffman et al, 2011), indicating their role in facilitating the preovulatory surge of GnRH (Clarke, 2017).…”

Section: Introductionmentioning

confidence: 96%

“…Whereas the Kp neurons of the arcuate nucleus come into close association with GnRH neuronal terminals in the median eminence ( Smith et al 2011 , Clarke 201 5), a second population of Kp neurons is found in the preoptic area of the ruminant ( Franceschini et al 2006 , Hassaneen et al 2016 ). These rostrally located Kp neurons, along with GnRH neurons in the same region, display Fos labelling after the start of the GnRH surge ( Hoffman et al 2011 ), indicating their role in facilitating the preovulatory surge of GnRH ( Clarke 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Onset of normal cycles in postpartum anovulatory dairy cattle treated with kisspeptin

Burke

Roche

Millar

et al. 2022

Reproduction and Fertility

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The efficacy of a long-acting synthetic derivative of kisspeptin (Kp) to initiate normal estrous cycles was tested in 24 mixed-aged, Holstein-Friesian cows that were 18 to 25 d postpartum on day of treatment (D0). Groups of eight received saline (Sal) vehicle by intramuscular injection at 0800 and 1600 h (Sal-Sal), Kp at 800 h and vehicle at 1600 h (Kp-Sal) or Kp on both occasions (Kp-Kp). The Kp dose was 15 nmol per 60 kg body weight. The cows ovaries were examined daily by ultrasonography between D-4 and D14. Blood samples were collected from a tail vessel 0, 2, 4, 8, 10 and 12 h relative to the time of first injection for LH and FSH assay. Additional samples were collected daily from D-4 until D14 and D19, 22, 26 and 29 for progesterone assay. An LH surge-like response were observed in cows treated with Kp at 0800 h. Ovulation was consistently induced by Kp within 48 h when there was a dominant follicle of at least 10 mm in diameter on the ovaries (8/14), but in no cases (6/14) during a new wave of ovarian follicular development consisting of follicles <10 mm diameter. The subsequent ovulatory cycle was of normal length in most cases, as compared with short 8 to 12 d cycles observed in spontaneously ovulating cows. We conclude that Kp treatment can induce ovulation in postpartum dairy cows, with ensuing estrous cycles of normal length, if administered when a mature dominant follicle is present on the ovaries.

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Generation of the GnRH Surge and LH Surge by the Positive Feedback Effect of Estrogen

Cited by 6 publications

References 79 publications

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

The roles of kisspeptin in the mechanism underlying reproductive functions in mammals

The GLP-1 agonist, exendin-4, stimulates LH secretion in female sheep

Onset of normal cycles in postpartum anovulatory dairy cattle treated with kisspeptin

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