Hypothalamic oxytocin in the developing ovine fetus: interaction with pituitary–adrenocortical function

Abstract

Oxytocin (OT) stimulates corticotroph function in adult sheep, however, there is little information on OT synthesis and its potential involvement in hypothalamo-pituitary-adrenal (HPA) function in the fetus. The objectives of this study were to examine developmental changes in hypothalamic OT synthesis and to investigate the actions of OT on fetal corticotroph function. Hypothalami were removed at various stages of pre- and post-natal development. OT mRNA levels were measured using in situ hybridization. For in vitro studies, fetal pituitaries were removed on days 129 and 138 of gestation. Anterior pituitary cells were dispersed and cells were treated with different concentrations and combinations of OT, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and cortisol. OT mRNA was present in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by day 60 of gestation, and levels significantly increased at term. OT mRNA was present in parvocellular and magnocellular fields of the PVN. In vitro, OT stimulated adrenocorticotropin (ACTH) output in a dose-dependent fashion, but had no effect on cellular pro-opiomelanocortin (POMC) mRNA levels. There was no significant difference in corticotroph responsiveness to secretagogues between cells harvested at gestation day 129 or gestation day 138. Simultaneous exposure to CRH and OT stimulated increases in ACTH output that were significantly greater than for OT or CRH alone. However, no similar synergistic interaction existed between OT and AVP. Cortisol attenuated OT-stimulated ACTH output. In conclusion, hypothalamic OT mRNA increases at term and OT can stimulate ACTH output from fetal corticotrophs. Together, these data indicate that OT may be involved in the regulation of ACTH secretion in fetal sheep in late gestation.