PRIMING EFFECT OF LUTEINIZING HORMONE RELEASING FACTOR IN VITRO: ROLE OF PROTEIN SYNTHESIS, CONTRACTILE ELEMENTS, Ca2+ AND CYCLIC AMP

Pickering, A; Fink, George

doi:10.1677/joe.0.0810223

Cited by 81 publications

(45 citation statements)

References 17 publications

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“…In physiological conditions, this action of GnRH is critical during the preovulatory period in which each GnRH pulse induces secretion of LH and potentiation of the secretory effects of successive GnRH pulses, giving rise to a massive (ovulatory surge) release of LH [27]. GnRH self-priming is strictly dependent on: (a) E priming of gonadotropes [25]; (b) protein synthesis different from GnRH receptors [28]and LH itself [29]; (c) the presence of PR in the gonadotrope [13, 30, 31], and (d) cAMP stimulation [32]. …”

Section: Discussionmentioning

confidence: 99%

Tamoxifen Induces Gonadotropin-Releasing Hormone Self-Priming through an Estrogen-Dependent Progesterone Receptor Expression in the Gonadotrope of the Rat

Bellido

Mulas²,

Tena‐Sempere³

et al. 2003

Neuroendocrinology

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Tamoxifen (TX) is an antiestrogen with varying levels of antagonist/agonist activity on the reproductive axis of the rat. It has been reported that TX, in contrast to other selective estrogen receptor modulators (SERMs), increases the content of cytosolic estrogen receptors (ER) in the gonadotrope and induces gonadotropin releasing hormone (GnRH) self-priming in the absence of E. GnRH priming is believed to be a consequence of E-dependent progesterone receptor (PR) activation. The purpose of this study was to determine whether TX induces PR expression in the gonadotrope in an E-dependent manner, and whether the blockade of PR activation affects TX-dependent GnRH self-priming in ovariectomized (OVX) rats. Chronic OVX rats were injected (sc) over 3 days with 25 µg estradiol benzoate (EB), 3 mg TX, 0.5 mg RU58668, a ‘pure’ anti-E (aE), 2 mg RU38486, an anti-P at the receptor (aP), TX+aE and TX+aP. Controls were given 0.2 ml oil. While EB and TX increased mRNA for both PR A+B and PR B expression and the number and intensity of nuclei immunoreactive (IR) for PR in the gonadotrope, the aE and aP given alone had no effect on either PR mRNA levels or nuclear PR-IR. The aE reduced the effect of TX on PR expression (mRNA and nuclear IR) while the aP slightly reduced nuclear PR-IR only. In addition, pituitaries from each of the seven groups were incubated with: 10^–8M E₂, 10^–7M TX, 10^–8M aE, 10^–8M aP, TX+aE, TX+aP or medium alone, respectively. Pituitaries were tested for GnRH self-priming (two pulses of 15 min 1 h apart) and the secretion of LH and PRL determined by specific RIAs. Pituitaries from rats treated with EB and incubated with E₂ had increased basal and GnRH-stimulated luteinizing hormone (LH) and prolactin (PRL) secretion and GnRH self-priming. TX reduced basal and stimulated LH secretion, increased PRL secretion and induced a robust GnRH self-priming. All these effects of TX were blocked by the aE, while the aP blocked GnRH self-priming only. In conclusion, tamoxifen induced PR expression (mRNA and nuclear IR) in the gonadotrope in an E-dependent manner, while activation of these PR through intracellular signaling of GnRH induced GnRH self-priming.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen Induces Gonadotropin-Releasing Hormone Self-Priming through an Estrogen-Dependent Progesterone Receptor Expression in the Gonadotrope of the Rat

Bellido

Mulas²,

Tena‐Sempere³

et al. 2003

Neuroendocrinology

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“…The key differences between the releasing and self-priming actions of GnRH are that: i) GnRH priming, but not releasing, is dependent on protein synthesis (Fink & Pickering 1975, Pickering & Fink 1976a, 1979, Curtis et al 1985; ii) in contrast to the GnRHreleasing action, GnRH self-priming cannot be mimicked by K C depolarisation or Ca 2 ionophores (Pickering & Fink 1976b); iii) priming involves potentiation of the IP3 intracellular Ca 2 mechanisms and protein kinase C (Johnson et al 1988); and iv) priming involves activation of mitogen-activated protein (MAP) kinase (Pickering & Fink 1979, Curtis et al 1985, Mobbs et al 1990). …”

Section: Mechanisms Involved In Gnrh Self-primingmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming

Fink¹

2015

Journal of Endocrinology

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Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the 'chemical substances' (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology -the way that the brain controls endocrine glands and vice versa -revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris' major interest: hypothalamic-pituitary-gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals.

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“…with the increased responsiveness of gonadotroph cells to GnRH provokes a cascade of intracellular events including potentiation of inositol 1,4,5-triphosphate, intracellular calcium mechanisms and protein kinase C (Mitchell et al 1988, Johnson et al 1992, Ison et al 1993, Simpson et al 1993, Haisenleder et al 1997, Washington et al 2004, as well as the rearrangement of microfilaments and LH-positive secretory granules relative to the plasmalemma (Pickering & Fink 1979, Lewis et al 1985, Currie & McNeilly 1995, Crawford et al 2000 to facilitate the preovulatory LH surge. In the subsequent luteal phase, rising progesterone levels cause a reduction in GNRHR mRNA expression levels (Wu et al 1994, Nett et al 2002 and numbers (Laws et al 1990) and pulse frequency of GnRH and LH (ChabbertBuffeta et al 2000), as well as an increase in the LH pulse amplitude (Chabbert-Buffeta et al 2000, McCartney et al 2007).…”

Section: Regulation Of Gonadotrophins In the Possummentioning

confidence: 99%

Gene expression and secretion of LH and FSH in relation to gene expression of GnRH receptors in the brushtail possum (Trichosurus vulpecula) demonstrates highly conserved mechanisms

Crawford¹,

Heath²,

Haydon³

et al. 2009

Reproduction

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In eutherian mammals, the gonadotrophins (LH and FSH) are synthesized and stored in gonadotroph cells under the regulation of multiple mechanisms including GnRH. Very little is known about the regulation of gonadotrophin secretion and storage in pituitary glands of marsupials. This study revealed, using quantitative PCR and heterologous RIA techniques, that LHB mRNA expression levels remained constant over the oestrous cycle, regardless of the presence of a preovulatory LH surge, which is characteristic of a hormone secreted under regulation. Our sampling regime was unable to detect pulses of LH during the follicular phase, although GNRHR mRNA levels had increased at this time. Pulses of LH were, however, detected in the luteal phase of cycling females, in anoestrus females and in males. There was a positive correlation between gene expression of FSHB and plasma levels of FSH at different stages of the oestrous cycle and no pulses of FSH were detected at any time; all characteristics of a hormone secreted via the constitutive pathway. Using in situ hybridisation and immunohistochemistry methods, we determined that mRNA expression of LHB and FSHB, and protein storage of gonadotrophins exhibited a similar pattern of localisation within the pituitary gland. Additionally, sexual dimorphism of gonadotroph populations was evident. In summary, these findings are similar to that reported in eutherians and considering that marsupial evolution diverged from eutherians over 100 million years ago suggests that the regulation of gonadotrophins is highly conserved indeed.

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PRIMING EFFECT OF LUTEINIZING HORMONE RELEASING FACTOR IN VITRO: ROLE OF PROTEIN SYNTHESIS, CONTRACTILE ELEMENTS, Ca2+ AND CYCLIC AMP

Cited by 81 publications

References 17 publications

Tamoxifen Induces Gonadotropin-Releasing Hormone Self-Priming through an Estrogen-Dependent Progesterone Receptor Expression in the Gonadotrope of the Rat

Tamoxifen Induces Gonadotropin-Releasing Hormone Self-Priming through an Estrogen-Dependent Progesterone Receptor Expression in the Gonadotrope of the Rat

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming

Gene expression and secretion of LH and FSH in relation to gene expression of GnRH receptors in the brushtail possum (Trichosurus vulpecula) demonstrates highly conserved mechanisms

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