The preovulatory LH surge: A case of a neuroendocrine switch

doi:10.1016/1043-2760(95)95218-T

Trends in Endocrinology & Metabolism

Volume 6, Issue 7, September 1995, Pages 241-247

https://doi.org/10.1016/1043-2760(95)95218-T Get rights and content

Abstract

The preovulatory surge in LH is a unique endocrine event that involves a switch from the negative feedback effect of estrogen to a positive feedback effect. This occurs at both the level of the brain and that of the pituitary gland. Within the brain the mechanism appears to involve disinhibition of negative inputs to GnRH neurons, as well as stimulation of positive inputs. The positive feedback effects on the brain and the pituitary appear to be coordinated so that the effect of estrogen involves a number of time-delayed mechanisms.

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To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI).
Retrospective cohort study.
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A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019.
Ovulation induction with letrozole, followed by autologous IUI.
The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables.
A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group.
In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.
Nacido vivo asociado con pico niveles séricos de estradiol con letrozol en ciclos de inseminación intrauterina.
Identificar si el nivel sérico de estradiol (E2) el día del disparo de la gonadotropina coriónica humana (hCG) o el aumento de la hormona luteinizante (LH) (hCG-LH) se asoció con la tasa de nacidos vivos (LBR) durante la inducción de la ovulación (OI) o hiperestimulación ovárica controlada con letrozol seguida de inseminación intrauterina (IIU).
Estudio de cohorte retrospectivo.
práctica privada grande y multicéntrica.
Se evaluó un total de 2368 ciclos de IO-IIU en pacientes tratados con letrozol seguidos de IUI desde el 1 de enero de 2014 hasta el 31 de julio de 2019.
Inducción de la ovulación con letrozol, seguida de IIU autóloga.
la medida de resultado primaria fue el LBR en función del nivel de E2 sérico en el momento de la administración de hCG o el aumento de LH, ajustado a la edad, índice de masa corporal, el diámetro del folículo más grande y el número de folículos R14 mm de diámetro. La tasa de embarazo clínico en función del nivel de E2, la tasa de embarazo en función del diámetro del folículo dominante y las tasas de pérdida de embarazo fueron las variables de resultado secundarias.
Un total de 2,368 ciclos cumplieron los criterios de inclusión. Los resultados se evaluaron en los percentiles 25 (nivel E2, 110 pg/ml), 50 (157 pg/ml), 75 (225 pg/ml) y 90 (319 pg/ml). Los LBR oscilaron entre el 9.4 % y el 11.1 % en las cohortes E2 inferiores y entre el 12.5 % y el 13.5 % en las cohortes E2 superiores. El LBR fue significativamente mayor en la cohorte de mujeres con niveles más altos de E2 en todas las comparaciones de percentiles excepto en el percentil 90. El diámetro medio del folículo periovulatorio de ≥20 o <20 mm no se asoció de forma independiente con el LBR o la tasa de embarazo clínico, a pesar de un nivel medio de E2 significativamente más alto en el grupo de folículos más grandes.
En los ciclos de IO con letrozol seguidos de IIU, se encontraron LBR más bajos y tasas de embarazo clínico en mujeres con niveles de E2 más bajos que en aquellas con niveles de E2 más altos en los cuartiles de nivel de E2 de los percentiles 25, 50 y 75. Siempre que sea posible, retrasar la activación de hCG hasta que el nivel de E2 aumente después de la inhibición de la aromatasa y se acerque al nivel periovulatorio fisiológico puede mejorar las tasas de embarazo con letrozol seguido de IIU.
Estrus Synchronization in the Sheep and Goat
2021, Veterinary Clinics of North America - Food Animal Practice
Citation Excerpt :
FSH secretion stimulates follicular development and increases estradiol-17β secretion. As the estradiol-17β concentration increases, hypothalamic sensitivity to estradiol-17β decreases, which in turn increases GnRH and LH pulse frequency culminating in the LH surge.24,25 The first ovulation of the breeding season occurs after the LH surge, but resultant corpus luteal formation and diestrus is represented by a significantly shortened luteal phase26,27 with minimal progesterone production.28–31
Peptide Neuromodulation in Invertebrate Model Systems
2012, Neuron
Citation Excerpt :
The authors infer a loop wherein Bseg activity feeds back positively to permit its own concerted release of BUR and release of the proper behavioral sequence (Luan et al., 2012). In endocrinology, the classic example of a positive feedback system is the control of ovulation in mammals, in which the hypothalamus and ovary interact positively to generate the luteinizing hormone surge that coordinates ovulatory events (Clarke, 1995). A threshold level of estrogen is reached in the follicular phase of the ovarian cycle and this signals changes from a negative feedback to a positive one: it now activates cells within the brain, probably disinhibiting inhibitory systems and activating positive inputs including kisspetin and noradrenergic afferents to gonadotropin releasing hormone (GnRH) neurons (Smith et al., 2011).
Neuropeptides modulate neural circuits controlling adaptive animal behaviors and physiological processes, such as feeding/metabolism, reproductive behaviors, circadian rhythms, central pattern generation, and sensorimotor integration. Invertebrate model systems have enabled detailed experimental analysis using combined genetic, behavioral, and physiological approaches. Here we review selected examples of neuropeptide modulation in crustaceans, mollusks, insects, and nematodes, with a particular emphasis on the genetic model organisms Drosophila melanogaster and Caenorhabditis elegans, where remarkable progress has been made. On the basis of this survey, we provide several integrating conceptual principles for understanding how neuropeptides modulate circuit function, and also propose that continued progress in this area requires increased emphasis on the development of richer, more sophisticated behavioral paradigms.
Neuroendocrine control of reproduction
2012, Handbook of Neuroendocrinology
Reproduction is totally dependent upon the secretion of gonadotropin-releasing hormone (GnRH) from the brain. GnRH provides trophic support and acts as a secretagog for the release of gonadotropins from the pituitary gonadotropes. The GnRH cells project to the external zone of the median eminence and to the organum vasculosum of the lamina terminalis. The levels of GnRH within the cells of the hypothalamus provide some index of the amount of stored neuropeptide available for release. This is a function of the levels of synthesis of the peptide and the amount of storage in neurosecretory terminals. The administration of kisspeptin to acyclic, seasonally anestrous ewes causes ovulation. The mechanism for this appears to be stimulation of basal gonadotropic secretion and stimulation of estrogen secretion by ovarian follicles, which, in turn, act to cause positive feedback and an ovulatory LH surge. Although reproductive function depends on the stimulatory action of gonadotropin–releasing hormone (GnRH), original work in birds identified and isolated a peptide that inhibits gonadotropin release, named gonadotropin inhibitory hormone (GnIH).
Control of GnRH secretion: One step back
2011, Frontiers in Neuroendocrinology
Citation Excerpt :
This particular study compared responses in ovariectomised ewes within 1 h after a challenge with estrogen, which is considered to be a transient signal to activate the positive feedback mechanism [31]. This signal activates a chain of events, leading to a time-delayed surge in GnRH secretion [26]. This study contrasted the activational state of kisspeptin neurons in the ARC in ovariectomised ewes that were receiving chronic estrogen treatment as opposed to a transient challenge.
The reproductive system is controlled by gonadotropin releasing hormone (GnRH) secretion from the brain, which is finely modulated by a number of factors including gonadal sex steroids. GnRH cells do not express estrogen receptor α, but feedback is transmitted by neurons that are at least ‘one step back’ from the GnRH cells. Modulation by season, stress and nutrition are effected by neuronal pathways that converge on the GnRH cells. Kisspeptin and gonadotropin inhibitory hormone (GnIH) neurons are regulators of GnRH secretion, the former being a major conduit for transmission of sex steroid feedback. GnIH cells project to GnRH cells and may play a role in the seasonal changes in reproductive activity in sheep. GnIH also modulates the action of GnRH at the level of the pituitary gonadotrope. This review focuses on the role that kisspeptin and GnIH neurons play, as modulators that are ‘one step back’ from GnRH neurons.
Superovulatory response of Sistani cattle to three different doses of FSH during winter and summer
2006, Theriogenology
Objective of the present study was to investigate the effect of season and dose of FSH on superovulatory responses in Iranian Bos indicus beef cattle (Sistani). Cyclic cows, in summer (n = 16) and winter (n = 16), were assigned randomly to three dose-treatment groups of 120 (n = 10), 160 (n = 12) and 200 (n = 10) total mg of Folltropin-V with injections given twice daily for 4 days in decreasing doses. Estrous cycles were synchronized with two prostaglandin F_2α injections given 14 days apart. From day 5 after the ensuing cycle, daily ovarian ultrasonography was conducted to determine emergence of the second follicular wave at which time superovulation was initiated. Relative humidity, environmental and rectal temperatures were measured at 08:00, 14:00 and 20:00 h for the 3 days before and 2 days after the estrus of superovulation. Non-surgical embryo recovery was performed on day 7 after estrus. The effects of season, dose, time of estrous expression and all two-way interactions were evaluated on superovulatory responses: total numbers of CL, unovulated follicles (10 mm), ova/embryo, transferable and non-transferable embryos. Season (summer or winter), doses of Folltropin-V (120, 160 or 200 mg NIH) and time of estrous expression (08:00, 14:00 or 20:00 h) did not affect the number of transferable embryos (3.1 ± 0.58). When superovulatory estrus was detected at 08:00, a FSH dose effect was detected with the greatest numbers of CL (12.2 ± 0.87) and total ova/embryos (12.2 ± 1.46) occurring with 200 mg FSH (dose × time of estrous expression; P < 0.01).

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Trends in Endocrinology & Metabolism

Brief reviewThe preovulatory LH surge: A case of a neuroendocrine switch

Abstract

Mol Cell Endocrinol

Brain Res

Brain Res

Mol Brain Res

Brain Res

Brain Res

Domest Anim Endocrinol

Luteinizing hormone-releasing hormone peptidase activities in discrete hypothalamic regions and anterior pituitary of the rat: apparent regulation during the prepubertal period and first estrous cycle at puberty

Endocrinology

The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion

Endocr Rev

Effect of time after castration on secretion of LHRH and LH in the ram

J Reprod Fertil

Coordinate actions of calcium and protein kinase-C in the expression of primary response genes in pituitary gonadotrophs

Endocrinology

Functional ultrastructure of gonadotropes: a review

Morphine suppresses the proestrous surge of GnRH in pituitary portal plasma of rats

Endocrinology

GnRH synthesis, secretion and action and ovarian steroidal feedback

Gonadotrophin releasing hormone secretion in anoestrous ewes and the induction of GnRH surges by oestrogen

J Endocrinol

Variable patterns of gonadotropin-releasing hormone secretion during the estrogen-induced luteinizing hormone surge in ovariectomized ewes

Endocrinology

The Hypothalamo-Pituitary Axis

Evidence that the switch from negative to positive feedback at the level of the pituitary gland is an important timing event for the onset of the preovulatory surge in luteinising hormone

J Endocrinol

The temporal relationship between gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes

Endocrinology

Direct pituitary effects of estrogen and progesterone on gonadotropin secretion in the ewe

Neuroendocrinology

GnRH secretion throughout the ovine estrous cycle

Neuroendocrinology

Pituitary receptors for GnRH in relation to changes in pituitary and plasma gonadotropins in ovariectomized hypothalamo-pituitary disconnected ewes II: a marked rise in receptor number during acute feedback effects of estradiol

Biol Reprod

Analysis of the ratio of biological to immunological luteinizing hormone (LH) secreted during the oestrogen-induced LH surge in the ewe

J Endocrinol

Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle

Endocrinology

Preoptic catecholamine, GABA, and glutamate release in ovariectomized and ovariectomized estrogen-primed rats using a push-pull cannulae technique

Neuroendocrinology

Morphine inhibits electrically stimulated noradrenaline release from slices of rat medial preoptic area

Neuroendocrinology

Release of luteinizing hormone releasing hormone, β-endorphin and noradrenaline by the nucleus infundibularis/median eminence during periovulatory period in the sheep

Neuroendocrinology

Estradiol modulates protein kinase C activity in the rat pituitary in vivo and in vitro

Endocrinology

Changes in dopamine β hydroxylase (DBH) in the A1 noradrenergic cell group following estrogen injection [abst 145]

Brief review
The preovulatory LH surge: A case of a neuroendocrine switch