Endocrine Abstracts

The greatly improved survival of children and adolescents with malignancy now makes it important to assess the long-term adverse effects of cancer therapy. Loss of fertility is reported by cancer survivors to be a major concern. In women, this largely relates to gonadotoxicity of chemotherapy or local radiotherapy; uterine damage is less common and follows pelvic surgery or radiotherapy. All chemotherapeutic agents are gonadotoxic, but particularly the alkylating agents such a...

Although prolactin is well recognised as a cytokine, effects of hypoprolactinaemia on biological endpoints are not well described in humans. In-vitro and clinical studies suggest an influence on humoral and cell mediated immunity and autoimmunity. We studied basal and stimulated immune function in panhypopituitary adults with and without prolactin deficiency and age and gender matched healthy controls. The study was approved by hospital and local research ethics committees. Ni...

Oestrogen is an important regulator of the pituitary hormone prolactin (PRL) in vivo, although the regulation mechanism is poorly understood. Liganded oestrogen receptor (ER) synergises with the pituitary specific factor Pit-1 on the rat PRL promoter to facilitate chromatin looping and increased transcription; however, no such mechanism has been reported for the human PRL promoter, in which the ERE sequence is altered.In pituitary GH3 cells stably transf...

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

The neuroendocrine and immune systems are closely linked, and cytokines such as IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), secreted by immune cells or neighbouring pituicytes, may have important local effects on pituitary function to modulate endocrine mechanisms of regulation.We have analysed the transcriptional regulation of the human prolactin (hPRL) gene promoter by TNF-alpha. Using stably transfected GH3 cells expressing luciferase und...

Glucocorticoid actions in the brain are mediated by glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). MR and GR bind endogenously circulating glucocorticoids, share a hormone response element in DNA, and are co-expressed in neurons of the hippocampus and hypothalamus. This arrangement suggests MR and GR functionally cooperate in the regulation of gene expression though hitherto poorly described mechanisms. This possibility was previously exampled by the demon...