Endocrine Abstracts

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

Animal and clinical models of GHRH excess suggest that GHRH provides an important trophic drive to pituitary somatotrophs. Mice in which GHRH neurons have been ablated using a novel viral ion channel transgene (GHRH-M2 mice) show marked anterior pituitary hypoplasia and GH deficiency although GH cells are present. GHRH-M2 mice are also deficient in prolactin which is surprising as GHRH has little or no direct effect on PRL synthesis or release (Le Tissier, Mol Endo 19). In mic...

Diagnosing malignancy and assessing the prognosis of adrenocortical tumors is challenging. The aim is to identify molecular predictors of malignancy and of survival.Patients and methods: Of 153 unilateral adrenocortical tumors were studied by microarray (n=92) or RT-qPCR (n=148). A 2-gene predictor of malignancy was built using the disease-free survival as the end-point in a training cohort (n=47), then validated in an independent va...

Adrenocortical tumor (ACT) is a rare, heterogeneous malignancy whose pathogenesis is unclear. The oncoprotein PTHrP, found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the receptor PTH-R1. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinoma (ACC), 13 adrenocortical adenoma (ACA), and investigated the effects of PTHrP (1–34) on H295R c...

Changes in hormone output to regulate physiological processes is a feature of all endocrine systems, with the added complication that for many systems, the pattern as well as level of output, determines the response of target tissues. Periodic patterns of hormone secretion can occur over multiple time scales, from ultradian to circadian, infradian, and circannual and may be dependent on physiological status. The activity and output of lactotroph and somatotroph cells of the pi...

Pituitary hormones are released into the bloodstream in a pulsatile fashion in response to stimuli from their hypothalamic regulators. For efficient generation of hormone pulses, both the hypothalamic mechanisms and the pituitary target cells must exhibit a high degree of coordinated secretory activity. This is particularly important for the growth hormone (GH) axis since the target tissue responses are critically dependent on the temporal pattern of GH exposure, as well as th...

Benign adrenal tumors correspond to a spectrum of distinct tumors, including uni- and bilateral diseases with distinct morphological features, and various steroid hormone secretion types and levels. The aim is to study this variability at the molecular level using pan-genomic approaches.Methods: One hundred and forty six benign adrenal tumors, including adrenocortical adenomas (ACA, N=), primary macronodular adrenal hyperplasia (PMAH, N=), and primary pi...

The classical paradigm of lactotroph prolactin production and release is based around tonic inhibition by hypothalamic dopamine and stimulation by factors such as estrogen. We have recently shown that conditional ablation of pituitary androgen receptor (Foxg1-Cre ARKO) surprisingly does not change the concentration of circulating gonadotrophins but increases circulating prolactin in male mice; highlighting androgen signalling as a novel negative regulator of prolactin producti...

Background: Adrenocortical cancer (ACC) is an aggressive tumour with heterogeneous prognosis. Pan-genomic studies identified molecular subgroups of ACC, remarkably associated with outcome. For routine prospective use, targeted molecular measures are needed, combined into reasonably easy and cheap techniques. The aim was to develop and validate different combinations of targeted molecular markers reflecting the molecular subgroup, and compare their prognostic value to standard ...

Background: Glucocorticoids are prescribed for >3 months to 1% of the UK population, principally to control inflammation. In 10–30% of patients, chronic glucocorticoid treatment suppresses HPA axis activity, causing atrophy of the adrenals and a failure to mount an adequate response during stress (potentially fatal) and following treatment withdrawal. Understanding the mechanisms resulting in HPA axis failure may allow us to predict those at risk, inform treatment str...