Hypophysial Responses to Continuous and Intermittent Delivery of Hypothalamic Gonadotropin-Releasing Hormone

Belchetz, P. E.; Plant, T. M.; Nakai, Yoshikatsu; Keogh, E.J.; Knobil, E.

doi:10.1126/science.100883

Cited by 1,268 publications

(341 citation statements)

References 22 publications

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“…Haplogroup D2a1 is one of the most common haplogroup in Japanese men, and in fact is only observed in the Japanese male population. LH is produced from the stimulation of gonadotropin-releasing hormones, and LH induces testosterone biosynthesis and secretion by testicular Leydig cells (Belchetz et al, 1978;Smith & Vale, 1981). Hence, spermatogenesis ability is diminished under conditions of low LH levels.…”

Section: Discussionmentioning

confidence: 99%

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

et al. 2015

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SUMMARYThe association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (b = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels.

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Section: Discussionmentioning

confidence: 99%

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

et al. 2015

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“…It has been known for over two decades that sustained stimulation of gonadotropes with GnRH causes desensitization of GnRH-stimulated gonadotropin secretion (30), an effect that can be either exploited or avoided in clinical applications of GnRH analogues (12). The recent discovery that mammalian GnRH receptors do not show rapid homologous desensitization (3)(4)(5)(6)(7)(8) reveals that desensitization of GnRH-stimulated gonadotropin secretion must reflect changes distal to the receptor, as implied by earlier work showing that GnRH receptor regulation does not explain desensitization of gonadotropin secretion (5).…”

Section: Discussionmentioning

confidence: 99%

Rapid Down-regulation of the Type I Inositol 1,4,5-Trisphosphate Receptor and Desensitization of Gonadotropin-releasing Hormone-mediated Ca2+ Responses in αT3–1 Gonadotropes

Willars¹,

Royall²,

Nahorski³

et al. 2001

Journal of Biological Chemistry

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Despite no evidence for desensitization of phospholipase C-coupled gonadotropin-releasing hormone (GnRH) receptors, we previously reported marked suppression of GnRH-mediated Ca 2؉ responses in ␣T3-1 cells by pre-exposure to GnRH. This suppression could not be accounted for solely by reduced inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) responses, thereby implicating uncoupling of Ins(1,4,5)P 3 production and Ca 2؉ mobilization (McArdle, C. A., Willars, G. B., Fowkes, R. C., Nahorski, S. R., Davidson, J. S., and Forrest-Owen, W. (1996) J. Biol. Chem. 271, 23711-23717). In the current study we demonstrate that GnRH causes a homologous and heterologous desensitization of Ca 2؉ signaling in ␣T3-1 cells that is coincident with a rapid (t1 ⁄2 < 20 min), marked, and functionally relevant loss of type I Ins(1,4,5)P 3 receptor immunoreactivity and binding. Furthermore, using an ␣T3-1 cell line expressing recombinant muscarinic M 3 receptors we show that the unique resistance of the GnRH receptor to rapid desensitization contributes to a fast, profound, and sustained loss of Ins(1,4,5)P 3 receptor immunoreactivity. These data highlight a potential role for rapid Ins(1,4,5)P 3 receptor down-regulation in homologous and heterologous desensitization and in particular suggest that this mechanism may contribute to the suppression of the reproductive system that is exploited in the major clinical applications of GnRH analogues.

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“…These neurons signal to the pituitary via the decapeptide GnRH1 to effect the release of the gonadotropins, follicle stimulating hormone and luteinizing hormone, which in turn stimulate steroid production by the gonads. It has long been known that this release depends on coordinated, pulsatile GnRH1 release, not simply elevated levels (7,8), requiring some level of synchronization in the output of these neurons. Episodic activation of the pituitary gonadotropes has been observed in multiple vertebrate taxa, including mammals and fish (9)(10)(11)(12), however, mechanisms that underlie this required coordinated activity of GnRH1 neurons are unknown.…”

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confidence: 99%

Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

Juntti

et al. 2015

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

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Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction.transgenic | GnRH | gap junction | cichlid | electrophysiology

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Hypophysial Responses to Continuous and Intermittent Delivery of Hypothalamic Gonadotropin-Releasing Hormone

Cited by 1,268 publications

References 22 publications

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

Rapid Down-regulation of the Type I Inositol 1,4,5-Trisphosphate Receptor and Desensitization of Gonadotropin-releasing Hormone-mediated Ca2+ Responses in αT3–1 Gonadotropes

Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

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