Date of Award
Doctor of Philosophy
The purpose of the present study was to elucidate the mechanisms regulating function of the ovine fetal pituitary-adrenal axis by hypothalamic, pituitary and adrenal factors, and by locally produced growth factors. Specifically, the effects of corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and cortisol on CRH binding, levels of proopiomelanocortin (POMC) mRNA and adrenocorticotropin (ACTH) output from the fetal ovine anterior pituitary were evaluated in vitro. Further, expression of the insulin-like growth factor (IGF) genes and possible roles of IGFs in the ovine fetal pituitary-adrenal axis were examined.;Our studies provide the following results: (1) The number of CRH binding sites in the fetal anterior pituitary changed with gestation. CRH, AVP and cortisol all down-regulated CRH binding, which was accompanied by a decrease in responsiveness of the pituitary cells to CRH stimulation in terms of ACTH output. (2) CRH and AVP increased ACTH output but had no effect on the level of POMC mRNA from cultured term fetal anterior pituitary cells. Cortisol decreased both the basal output of ACTH and the level of POMC mRNA. (3) IGF-II mRNA, IGF-II peptide and IGF-I peptide were detected in the anterior pituitary tissue. IGF-I upregulated CRH binding in cultured anterior pituitary cells from term fetuses. However, IGFs had no effect on either ACTH output or the level of POMC mRNA. (4) IGF-I and IGF-II mRNAs and peptides were localized to the capsule and steroidogenic cells in the adrenal cortex and medulla.;We conclude: (1) CRH and AVP stimulate the output of ACTH at steps distal to transcription of the POMC gene. The lack of effect of CRH and AVP on transcription of the POMC gene and their negative effects on CRH binding suggests that other trophic factors may be involved in functional regulation of the pituitary. (2) Cortisol is a potent inhibitor of pituitary function as it decreases CRH binding, POMC mRNA level and ACTH output. (3) Both the pituitary and adrenal synthesize IGFs locally. IGFs may be important in the functional regulation of the adrenal, rather than of the pituitary component of the fetal hypothalamic-pituitary-adrenal axis.
Lu, Feng, "Functional Regulation Of The Pituitary-adrenal Axis In The Ovine Fetus" (1994). Digitized Theses. 2458.