Endocrine Abstracts

AZP-3601, a long-acting PTH/PTHrP(1-36) analog, is a candidate new treatment option for hypoparathyroidism (HP). As compared to conventional PTH(1-34), AZP-3601 binds with higher affinity to the R0 conformation of the PTH-1 receptor, resulting in prolonged signaling and sustained elevations in blood calcium (Ca++) in vivo, despite a very short circulating half-life. We assessed whether repeated injection of AZP-3601 into TPTX rats at doses aimed to normalize serum C...

In human GL cells, 11beta-HSD catalyses the interconversion of cortisol (F) with its inert 11-ketosteroid metabolite, cortisone (E). Since GL cells synthesise prostaglandins (PGs), and PGs have been shown to modulate the expression and activity of the cloned 11beta-HSD enzymes, the objective of the present study was to establish whether locally synthesised PGs affected the net oxidation of F to E by 11beta-HSD in human GL cells recovered from the ovaries of women undergoing co...

Clinical CaseA 19-year old ethnic Pakistani presented with severe, longstanding hirsutes without virilisation. Menarche had occurred at age 14, following which she had experienced 4-6 periods a year. She had always been “underweight” by UK/WHO criteria and, given a BMI of 16.5 kg.m−2, there were concerns about hypothalamic oligomenorrhoea.InvestigationsFasting glucose 5.5 mmol/L &#...

In human granulosa-lutein (hGL) cells, cortisol (F) is inter-converted with cortisone (E) by 11BHSD. To date two isoforms of 11BHSD have been cloned. Human granulosa cells have been shown to express 11BHSD2 mRNA during the follicular phase of the ovarian cycle, switching to 11BHSD1 mRNA expression as luteinization occurs. However, it is not known whether (1) the protein expression, and (2) the 11BHSD enzyme activities reflect this pattern of mRNA expression. Hence, the aims of...

PGE2 stimulates progesterone synthesis in the primate corpus luteum, apparently via cAMP. Human GL cells express functional EP1 and EP2 receptors via which PGE2 elevates the intracellular calcium and cAMP concentrations respectively (Harris et al, 2001, BBRC 285:1089). In the present study, we have determined the involvement of EP1 and EP2 receptors in the stimulation of cAMP accumulation and progesterone synthesis in these human ovarian cel...

Medical treatment of acromegaly is based on either suppressing pituitary GH secretion or inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of IGF1. AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) derived from peptide sequences discovered using a unique, cell-free in vitro transcription-translation system screened against the human GHR, and that was optimized by rational design to increase...

The key metabolic hormone, leptin, acts in part through the liver to regulate glucose homeostasis, as well as the maturation of both adipocytes and osteoblasts. These actions have been demonstrated to be mediated by insulin-like growth factor binding protein 2 (IGFBP-2), independent of its ability to bind IGF1. The effects of IGFBP-2 on adipocyte and osteoblast maturation can be localized to a short peptide sequence within the unique heparin binding domain (HBD-1) of IGFBP-2. ...

Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bi...

Eneboparatide (AZP-3601) is a novel, synthetic, 36-amino-acid peptide agonist of the parathyroid hormone type 1 receptor (PTHR1), with potent selectivity for the R0 conformation. This results in prolonged calcemic responses, while having a short circulating half-life. Eneboparatide is being developed for the treatment of chronic hypoparathyroidism (cHP). Studies in hypoparathyroid animal models and, most recently, in hypoparathyroid patients, have demonstrated that eneboparati...

Medical treatment of acromegaly is based on either suppressing pituitary growth hormone (GH) secretion or by inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of insulin-like growth factor 1 (IGF1). AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) with KD of 1.9 nM for the human GHR. Previously, AZP-3813 was demonstrated to suppress IGF1 secretion in juvenile rats in a dose-rela...