Endocrine Abstracts

Prolactin secretion is sexually dimorphic and sensitive to changes in gonadal steroid and glucocorticoid status. Reports that the regulatory effects of glucocorticoids on prolactin release are mediated in part via annexin 1 (ANXA1, 1), have led us to compare prolactin secretion and lactotroph morphology in ANXA1 knockout (KO) and wildtype (WT) mice and to determine the effects gonadectomy +/- testosterone replacement (80 micrograms per day, s.c.) on (a) the plasma prolactin concentration (radioimmunoassay) and (b) the number of tyrosine hydoxylase (TH) positive cells (immunocytochemistry) in the hypothalamic arcuate and periventricular nuclei (AN & PN). The plasma prolactin concentration was raised and pituitary prolactin content reduced in male ANXA1 KO mice vs. WT controls (P<0.05). No such differences were evident in the female and lactotroph morphology was unchanged in mice of either sex by ANXA1 gene deletion. In male WT mice, gonadectomy produced an increase in plasma prolactin which was unaffected by testosterone replacement. By contrast, in the ANXA1 KO plasma prolactin was unaffected by gonadectomy but increased by testosterone replacement. ANXA1 gene deletion did not affect TH-positive cell number in the AN or PN. In the AN, TH-positive cell number was unaffected by gonadectomy in KOs and WTs but increased by testosterone replacement (P<0.05) in WT but not KO mice. In contrast, in both mouse strains TH-positive cell number in the PN was increased by gonadectomy (P<0.05) but unaffected by testosterone replacement.

These results indicate that (a) ANXA1 gene deletion causes alterations in the hypothalamo-pituitary prolactin axis and its sensitivity to gonadectomy and testosterone replacement and (b) testosterone exerts differential effects on TH expression in the PN and AN. The interactions of ANXA1 and gonadal factors in the regulation of prolactin release require further study.

1. John CD et al (2004). TEMS 15, 103-109.

Generously supported by the Wellcome Trust.