The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH), acting via its receptors (GnRHRs) expressed in pituitary gonadotrophs, represents a critical molecule in control of reproductive functions in all vertebrate species. GnRH-activated receptors regulate synthesis of gonadotropins in a frequency-dependent manner. The number of GnRHRs on the plasma membrane determines the responsive...

Biallelic, partial loss-of-function mutations in GNRHR cause a wide spectrum of reproductive phenotypes from constitutional delay of growth and puberty to complete congenital hypogonadotropic hypogonadism. We studied the frequency of GNRHR, FGFR1, TAC3, and TACR3 mutations in nine adolescent and young adult females with clinical cues consistent with partial gonadotropin deficiency (stalled pube...

Gonadotropin-releasing hormone (GnRH) acts via seven transmembrane receptors to stimulate gonadotropin secretion. Sustained stimulation desensitizes GnRH receptor (GnRHR)-mediated gonadotropin secretion, and this underlies agonist use in hormone-dependent cancers. Since type I mammalian GnRHR do not desensitize, agonist-induced internalization and downregulation may underlie desensitization of ...

Human gonadotropin-releasing hormone receptor (GnRHR) and its natural ligand human gonadotropin-releasing hormone (GnRH) were initially described as signaling complexes that play a key role in reproductive functions. By binding to specific receptors present on pituitary gonadotropes, GnRH regulates the sperm and ovum maturation, as well as steroidogenesis within the context of the hypothalamus-...

BACKGROUND Regulation of gonadotropin-releasing hormone (GnRH) receptor (GnRHR) numbers on gonadotropes within the anterior pituitary gland represents a critical point for control of reproductive function. Binding of GnRH to its receptor regulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and levels of this G-protein coupled receptor on the surface of gonadotropes ...

BACKGROUND Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we characterized chromatin structure changes, ...

BACKGROUND The Foxl2 transcription factor is required for ovarian function during follicular development. The mechanism of Foxl2 regulation of this process has not been elucidated. Our approach to begin to understand Foxl2 function is through the identification of Foxl2 regulated genes in the ovary. METHODS Transiently transfected KK1 mouse granulosa cells were used to identify genes that are...

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.[Asn10Lys;Gln11Lys]; [Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed...

Homologous regulation of GnRH receptor (GnRHR) gene expression is an established mechanism for controlling the sensitivity of gonadotropes to GnRH. We have found that expression of the GnRHR gene in the gonadotrope-derived alpha T3-1 cell line is mediated by a tripartite enhancer that includes a consensus activator protein-1 (AP-1) element, a binding site for SF-1 (steroidogenic factor-1), and ...

OBJECTIVE Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH) and, unlike Kallmann syndrome, is associated with a normal sense of smell. Mutations in the GNRHR gene cause autosomal recessive nCHH. The aim of this study ...