Endocrine Abstracts

An aspiration for many young researchers is to continue training beyond an advanced degree in another country. The current J-1 exchange visa, available to UK citizens for up to five years, provided a gateway for my exciting opportunity to pursue a career in the US. Attending international conferences, such as ENDO and BES, allowed me to identify research groups that were aligned with my interests and ambitions, setting the stage to apply and ultimately begin my current positio...

CNP, the third peptide of the mammalian natriuretic peptide family, exerts its biological effects through activation of the guanylyl cyclase B (GC-B) receptor and resulting cGMP accumulation. Our previous studies reported that CNP stimulates phosphorylation of MAPK family proteins in GH3 somatotrophs. This present study aimed to further characterise the mechanism of CNP-stimulated ERK phosphorylation and resulting biological consequences in GH3 cells. Western blot analyses sho...

Natriuretic peptides, ANP, BNP and CNP, exert the majority of their effects via particulate guanylyl cyclase receptors (GC-A or GC-B), resulting in increased cellular cGMP levels. Several studies have examined the pharmacological properties of GC-B receptors in many systems, and desensitization (tachyphylaxis, loss of response) has been reported to occur. Targeted deletion (in mice) or genetic mutations (in humans) of the GC-B receptor have been implicated in a dwarfism phenot...

Gonadotrophs have previously been shown to be the predominant source of C-type natriuretic peptide (CNP) in the anterior pituitary, and CNP causes enhanced cGMP accumulation in αT3-1 gonadotrophs. However, the biological role of CNP in gonadotrophs remains elusive. In the current study, we examined the molecular and functional characteristics of the gonadotroph natriuretic peptide system. Using two well-characterised gonadotroph cell lines of different developmental origi...

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...

CNP, the third member of the mammalian natriuretic peptide family, exerts the majority of its biological effects via the guanylyl cyclase B (GC-B) receptor, resulting in accumulation of intracellular cGMP. Previous studies reveal numerous inhibitory effects of natriuretic peptides on the MAPK family in bone, neuronal and cardiovascular tissues. However, we recently reported that CNP stimulates ERK, p38MAPK and JNK phosphorylation in pituitary GH3 somatotrophs. As CNP is known ...

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...

Cannabinoids are known to exert effects throughout the endocrine system, including in the anterior pituitary. Whilst cannabinoid receptors (CB1 in particular) are expressed in numerous tissues, expression and function of an endocannabinoid system within specific anterior cell types has not been investigated. We have used well-characterised gonadotroph (LβT2 and αT3-1) and somatolactotroph (GH3) cell lines to establish the expression and functional role for cannabinoi...

Despite being identified almost two decades ago, the biological roles for C-type natriuretic peptide (CNP) have remained poorly elucidated. Both CNP and GC-B are highly conserved from flies and fish to humans. Recent investigations involving the disruption of the CNP gene (Nppc) or that of its GC-B receptor (Npr2) implicate a role for CNP and GC-B in bone formation and growth. Intriguingly, CNP and GC-B knock-out mouse models also exhibited pituitary growth hormone deficiency....

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...