Endocrine Abstracts

Regulation of many pituitary-specific genes involves calcium signalling, yet the mechanisms and signalling molecules involved have yet to be established. CaMK's are expressed in a wide variety of tissues, and are known to modulate transcriptional regulators such as MAPK's and CREB. It is unclear as to which anterior pituitary cell types express CaMK's, or which isoforms are present. We have examined the presence and localisation of type II and IV CaMK's in alphaT3-1, LbetaT2 (...

Bone morphogenetic protein-2 (BMP-2) signal transduction requires heterocomplexing between type II receptors and different type I (α or β) receptors resulting in the activation of different signalling pathways. Previously, we have used αT3-1 and Lβt-2 cell lines, which are representative of different stages of gonadotroph development, to demonstrate differential expression of the receptor isoforms during gonadotroph maturation. BMPR-Iα and II mRNA and ...

Liver X receptors α and β (NR1H3 and NR1H2) play major a role within cells and tissues involved in lipid metabolism and cholesterol homeostasis including macrophages, the liver and the small intestine. Within the skin however, the roles of LXR are less well documented, although in vitro studies using primary human keratinocytes have implemented LXR in the formation of the stratum corneum via the increase of transcription of the proteins involved in the AP-1 co...

The local expression of bone morphogenetic protein-2 (BMP-2) during pituitary development mediates the commitment of undifferentiated cells to the gonadotroph lineage. In the current study, we have used alphaT3-1 and LbetaT2 cells, which represent different stages of gonadotroph development to examine BMP-2 receptor (BMPR) expression and effects of BMP-2 on cell signalling pathways and cell proliferation. In bone, signal transduction via BMPRs requires heteromeric complexing b...

Human skin is a target tissue for circulating androgens released from the adrenal glands and gonads but local steroid production may also occur in human skin. StAR is a cholesterol transporter protein that controls the rate-limiting step in steroid synthesis and is regulated by steroidogenic factor (SF-1) in the adrenal glands. We have demonstrated the expression of StAR mRNA by RT-PCR in primary dermal papilla cells and in the immortalised human keratinocyte cell line HaCaT. ...

The orphan nuclear receptor, steroidogenic factor-1 (SF-1) regulates gonadotroph development and gene expression. In the absence of an identified ligand, SF-1 has been shown to be constitutively active and recent studies reveal that post-translational modification may regulate its transcriptional activity. The Ser 203 residue, proximally located to helix 1 of the ligand binding domain (LBD) of SF-1, resides in a consensus MAPK phosphorylation site, and is required for full tra...

SHOX has been implicated in the regulation of bone growth and modelling. Haploinsufficiency and heterozygous mutations of SHOX are associated with Lerri Weil Dyschondrosteosis (LWD). The cardinal features of LWD are mesomelic limb shortening and Madelung deformity. Histological studies demonstrate premature fusion of the ulna border of the radial epiphysis and disordered osteoblast maturation and orientation. In view of these observations we investigated the role of SHOX in th...

The cellular and molecular mechanisms underlying the actions of BMP-2 to induce gonadotroph-specific gene expression during pituitary development are poorly understood. We have characterised BMP receptor (BMP-R) expression in two gonadotroph models, the alphaT3-1 and LbetaT2 cells, which represent different stages of gonadotroph development. Signal transduction via BMP-R requires a heterodimeric complex between type I (A or B) and type II receptors. RT-PCR for BMP-R, using sub...

BACKGROUND: Ghrelin is a novel 28-amino acid peptide which was isolated from the rat stomach and has now been shown to have a widespread tissue distribution. Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a), and stimulates growth hormone (GH) release via the hypothalamus as well as by a direct action on the pituitary GHS-R1a. Ghrelin and the GHS-R1a also coexist within the pituitary. There are conflicting data regarding the effects...