title: Studies of the regulation of the hypothalamic-pituitary-adrenal axis in sheep with hypothalamic-pituitary disconnection. II. Evidence for in vivo ultradian hypersecretion of proopiomelanocortin peptides by the isolated anterior and intermediate pituitary.
abstract: Studies were performed to determine whether the isolated ovine anterior and intermediate pituitary might rhythmically secrete three POMC peptides, ACTH, ir-beta-endorphin (ir-beta-EP), and ir-alpha-melanocyte stimulating hormone (ir-alpha-MSH) in vivo. When blood was taken at 10-min intervals from four ewes with hypothalamo-pituitary-disconnection (HPD), a distinct POMC-peptide and cortisol ultradian rhythm was noted. A comparison of the four HPD ewes with five nonstressed hypothalamopituitary-intact (HPI) ewes revealed that the mean plasma levels of the three POMC-peptides and cortisol were increased, the mean ACTH and ir-alpha-MSH pulse amplitudes were increased, and the mean ir-beta-EP and ir-alpha-MSH interpulse intervals were decreased. When four HPI ewes were subjected to a mild stress, plasma POMC-peptide and cortisol levels increased significantly when compared with the five unstressed HPI animals. In addition, the ACTH and cortisol pulse amplitudes increased and the ir-beta-EP and ir-alpha-MSH interpulse intervals decreased. Although plasma ACTH levels in the stressed HPI and HPD ewes were comparable, mean plasma cortisol levels were 2-fold greater in the stressed HPI animals. To determine whether the ACTH hypersecretion in the HPD ewe might reflect a net reduction in hypothalamic inhibitory influence over ACTH secretion, we examined the effects of dopamine (DA), somatostatin (SS-14), and rat atrial natriuretic peptide [rANF(1-28)] on the secretion of ACTH from cultured ovine anterior pituitary cells. DA and SS-14 did not exert a discernible effect on basal, CRF-, or arginine vasopressin (AVP)-stimulated ACTH secretion. Although basal ACTH secretion was unaffected by rANF(1-28) (10(-12)-10(-8) M), a significant inhibition of CRF- and AVP-stimulated ACTH release was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Prince Henry's Institute of Medical Research, South Melbourne, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Engler
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: J P
authors.initials: JP
authors.lastname: Liu
authors.forename: M J
authors.initials: MJ
authors.lastname: Fullerton
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000502:physiology* / Q000601:surgery; D010507:Periodicity; D010902:Pituitary Gland / Q000502:physiology* / Q000601:surgery; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D012756:Sheep; D013004:Somatostatin / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D013004:Somatostatin; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D004298:Dopamine; D006854:Hydrocortisone