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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
After secretion into the bloodstream, GnRH travels via the portal blood to the pituitary gland where it acts on its own receptor known as the Gonadotropin-Releasing Hormone Receptor (GnRHR), a seven-transmembrane G-Protein-Coupled receptor (Figure 8.24). This stimulates production of the beta-isoform of Phosphoinositide Phospholipase C, which then mobilizes calcium and Protein Kinase C. This results in the activation of proteins involved in the synthesis and secretion of the two pituitary hormones, Luteinizing Hormone and Follicle-Stimulating Hormone from the anterior pituitary. These hormones induce the production of estrogen and progesterone in the ovaries in females, and testosterone in the testes in males. This, in turn, induces ovulation in females and gametogenesis in males. GnRH is the target of various regulatory processes within the hypothalamic–pituitary–gonadal axis, and is inhibited by rising levels of estrogen or testosterone in females and males, respectively (i.e., via a feedback loop).
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
As indicated in a recent review [64], three GnRH receptors or receptor-like sequences have been identified, with distinct distributions and functions. The GnRHR type I is the predominant form in mammalian gonadotrophs. In some species, including humans, GnRHR-1 is also expressed in reproductive tissues (e.g., breast, endometrium, ovary, prostate) and in tumors derived from these tissues. GnRHR is a 60 kDa, G protein-coupled receptor, whose number in the gonadotrophs depends on the developmental and reproductive stage and determines their responsiveness to GnRH. Receptor number is regulated at the transcriptional level by estradiol (E2) and the pattern of GnRH pulsatility. Transcription of Gnrhr in cultured gonadotrophs occurs in the absence (basal) and presence (regulated) of GnRH stimulation.
The inherited basis of hypergonadotropic hypogonadism
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
GnRH is crucial for regulating reproduction in mammals. It is synthesized by hypothalamic neurons and released from nerve endings into the portal circulation. After binding to the membrane GnRHR type 1 receptor, it stimulates gonadotropic cells of the anterior pituitary to synthesize and release LH and FSH, which in turn, stimulate synthesis and secretion of sex steroid hormones, and gametogenesis. Proof that GnRH mutations are involved in CIHH pathogenesis appeared in two reports in 2009.72,73
Activation of Gonadotropin-releasing Hormone Receptor Impedes the Immunosuppressive Activity of Decidual Regulatory T Cells via Deactivating the Mechanistic Target of Rapamycin Signaling
Published in Immunological Investigations, 2022
Xuejin Wang, Liangying Zhong, Qiaodan Liu, Peiya Cai, Peiru Zhang, Zhilan Lu, Xiaoqin Li, Jin Liu
Gonadotropin-releasing hormone receptor (GnRHR) is mainly expressed on pituitary gonadotrope cells. Its ligand, GnRH, is secreted by hypothalamus, pituitary, and non-hypothalamic reproductive tissues such as ovaries, placenta, endometrium, oviducts, testes, prostrate, and mammary glands (Ramakrishnappa et al. 2005). In contrast with non-pregnant women, GnRH is measurable with pulsatile fluctuations in maternal blood during pregnancy (Petraglia et al. 1994). Upon binding to gonadotropin-releasing hormone (GnRH), GnRHR is activated to regulate the synthesis and secretion of the gonadotropins (Flanagan and Manilall 2017). Previous studies indicated the presence of GnRHR mRNA in human peripheral blood mononuclear cells (Chen et al. 1999). Recent studies suggested that GnRHR agonists might induce pro-inflammatory differentiation of T cells (N. Sung et al. 2015, 2016). However, the role of GnRHR in the modulation of immune cell functions is poorly understood. Particularly, the effect of GnRHR on the development and immunosuppressive activity of Tregs remains completely unknown.
Buserelin Inhibits the Immunosuppressive Activity of Regulatory T Cells through the Protein Kinase A Signaling in a Central Precocious Puberty Model
Published in Immunological Investigations, 2022
Hua Li, Xiao-Xia Zhu, Jin-Bo Xiang, Lei Jian
Central precocious puberty (CPP) is caused by the premature activation of the hypothalamic-pituitary-gonadal axis (HPG) (Eugster 2019). Safe and effective therapy of CPP with GnRH analogs (GnRHas) has been performed for many years (Wang et al. 2016). GnRHas activate the HPG axis to induce a paradoxical downregulation and subsequent suppression of the HPG axis, thus arresting pubertal progression (Belchetz et al. 1978). Buserelin, a GnRH agonist, has been used to treat CPP for decades. However, the potential effects of GnRHas on other tissues besides the HPG axis remain largely elusive. The mRNA of GnRH receptor (GnRHR) has been found in the murine ovary, testis, uterus, and heart (Torrealday et al. 2013). Moreover, human peripheral blood mononuclear cells express GnRHR (Chen et al. 1999). Therefore, GnRHas might influence the function of various organs and tissues including the immune system. Indeed, recent studies have indicated that buserelin leads to pro-inflammatory differentiation of T cells and induces Th1 and Th17 immunity (Sung et al. 2016, 2015). Thus, GnRHas might modulate the functions of immune cells including T cells.
Prevalence of primary aldosteronism without hypertension in the general population: Results in Shika study
Published in Clinical and Experimental Hypertension, 2018
Shigehiro Karashima, Mitsuhiro Kometani, Hiromasa Tsujiguchi, Hiroki Asakura, Shigeru Nakano, Mikiya Usukura, Shunsuke Mori, Masashi Ohe, Toshitaka Sawamura, Rika Okuda, Akinori Hara, Toshinari Takamura, Masakazu Yamagishi, Hiroyuki Nakamura, Yoshiyu Takeda, Takashi Yoneda
There have been previous reports of aberrant G-protein-coupled receptors (including luteinizing hormone-chronicgonadtropin receptor (LHCGR) and gonadotropin-releasing hormone receptor (GnRHR) in both human normal adrenal tissue and APA (34–38). It is quite possible that high levels of LH and GnRH after menopause cause aldosterone over-production from the adrenal gland in a subtype of normotensive PA.