Endocrine Abstracts

The promiscuous low affinity neurotrophin co-receptor p75NTR, a member of the nerve tumor necrosis factor (TNF) receptor superfamily, mediates neuronal survival as well as death, and interacts with Trk receptors to increase their affinity for neurotrophins. Furthermore, p75NTR is the transmembrane signalling moiety which associates with the NOGO binding receptor for all CNC myelin-derived axon growth inhibitors in the injured CNS. We have shown in rats that intravitreal implan...

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...

Immunoneutralisation and antisense studies have shown that the acute regulatory actions of glucocorticoids (GCs) on the secretion of corticotrophin (ACTH) from the anterior pituitary gland are dependent upon the 37 kDa protein, annexin 1 (Anxa1 [1]), which is localised mainly to the S100-positive folliculo-stellate (FS) cells that lie in close apposition with the endocrine cells. The aim of this study was to examine pituitary function in male and female mice lacking the Anxa1 ...

Hypothalamic Cocaine- and Amphetamine-regulated transcript (CART) is regulated by circulating glucocorticoids. In adrenalectomised rodents, CART expression is reduced in the arcuate nucleus. However, CART also modulates the hypothalamo-pituitary-adrenal (HPA) axis. Acute intracerebroventricular injection of CART peptide significantly increases plasma ACTH and corticosterone but the long-term actions of CART are unknown. The aim of these studies was to determine the effect of l...

The pro-opiomelanocortin (POMC)-derived peptides, pro-gamma-MSH and Lys-gamma3-MSH, have been shown to potentiate the steroidogenic action of Adrenocorticotropic hormone (ACTH) on the adrenal cortex. The molecular mechanisms for this potentiation are unclear, but it has been shown that gamma-MSH peptides promote mitochondrial cholesterol accumulation in the adrenal cortex by upregulating the activity of Hormone Sensitive Lipase (HSL) (1). HSL activity is regulated either by up...

We report the efficacy, safety, and effects on glucose homeostasis of converting patients with acromegaly from slow release octreotide (OT, treated for >3 months) to pegvisomant (Peg), a GH receptor antagonist. 52 patients (median age 49, range 23-81, 13 with diabetes) who had previously participated in a Peg clinical trial and subsequently treated with OT were enrolled in a 32-week, open-label, multicentre study. Peg 10 mg/d was started 4 weeks after the last dose of OT (w...

Introduction: Lanreotide Autogel(R) is a long-acting somatostatin analogue preparation that is presented in pre-filled syringes for deep subcutaneous (sc) injection. The efficacy and tolerability of lanreotide Autogel given in titrated doses (ATG-TITRATE) for the treatment of acromegaly was assessed during this study.Methods: The study extended an existing study, during which fixed doses of lanreotide Autogel (ATG-FIX, 60, 90 and 120 mg) were ...

Cocaine and amphetamine regulated transcript (CART) is a hypothalamic neuropeptide with a role in the hypothalamo-pituitary adrenal axis (HPA) in rodents. However, the role of pituitary CART is poorly understood. Previous work in rodents has shown pituitary CART is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. CRH increased pituitary CART release fifteen-fold. Adrenalectomised rats had significantly higher pituitary CART mRNA expression, pituitary CA...