Endocrine Abstracts

The hypothalamic-pituitary-gonadal (HPG) axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory neuroendocrine factors. Delayed or absent activation of the HPG axis results in delayed puberty or hypogonadotropic hypogonadism, whereas early activation results in central precocious puberty (CPP). In recent years, many genes have been identified in this complex network from genetic studies of human subjects with pubertal ...

The mechanisms controlling the timing of puberty remain largely unknown. Recent insights into genetic causes of pubertal disorders have provided important advances in our understanding of the physiology underlying this developmental process. Mutations in genes important in neuroendocrine pathways controlling GnRH release and LH and FSH secretion have been identified in patients with isolated hypogonadotropic hypogonadism, Kallmann syndrome, and central precocious puberty. Many...

The hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), is the key neuroendocrine regulator of mammalian reproductive development and function. GnRH binds to its target, the GnRH receptor (GnRHR), on pituitary gonadotropes to stimulate the synthesis and intermittent release of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate gametogenesis and gonadal hormone synthesis. Thus GnRH, via the GnRHR, plays a piv...

GnRH is released from the hypothalamus in a pulsatile manner and binds to specific receptors (GnRHR) in the anterior pituitary gland to stimulate follicle-stimulating hormone (FSH) and luteinizing hormone (LH) subunit gene expression and subsequent FSHβ and LHsecretion. The FSH and LH subunits are preferentially stimulated by pulsatile GnRH at low and high pulse frequencies, respectively. The transcription factors, cAMP response element binding protein (CREB) and inducibl...

The pulsatile release of GnRH regulates the synthesis and secretion of pituitary FSH and LH. Two transcription factors, the cAMP response element binding protein (CREB) and inducible cAMP early repressor (ICER), have been implicated in the regulation of rat FSHβ gene expression. We hypothesized that CREB and ICER are activated by distinct signaling pathways in response to pulsatile GnRH to modulate FSHβ gene expression, which is preferentially stimulated at low (ever...

Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regulated by pulsatile GnRH secretion and its action on the anterior pituitary, leading to the synthesis and secretion of LH and FSH. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH/lH pulse generator and are key regulators of puberty and fertility. The HPG axis is active during prenatal and early postnatal life in humans and rodents, but then remains quiescent until puberty in both ...

The pathogenesis of pituitary adenomas is poorly understood. One of the first genetic abnormalities identified in association with pituitary adenomas occurs in patients with multiple endocrine neoplasia type-1 (MEN-1), due to mutations in the MEN1 gene, encoding menin. A tumor suppressor, menin associates with histone methyltransferase complexes to change the expression of cyclin-dependent kinase (CDK) inhibitor genes, which may serve as an underlying epigenetic mecha...

Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3’-untranslated region (UTR), operates as repressor of Mkrn3 to control pube...