The effect of hypothalamo-pituitary disconnection on the functional and morphologic development of the pituitary-adrenal axis in the fetal sheep in the last third of gestation.
We have investigated the effect of hypothalamo-pituitary disconnection (HPD) on the maturation of basal ir-ACTH and cortisol concentrations in fetal sheep plasma, and on the development of the anterior pituitary corticotroph population in the last third of gestation. After HPD, fetal plasma ir-ACTH concentrations were significantly elevated, and continued to rise with increasing gestational age. However, despite elevated ir-ACTH concentrations, there was no increase in fetal plasma cortisol concentrations, and parturition was delayed for at least 8 days beyond normal term. Furthermore, HPD resulted in a significant disruption of the maturation of the pars distalis corticotrophs. We also examined the change in fetal plasma concentrations of ir-ACTH and cortisol to exogenous CRF after HPD. There was a significant increase in plasma ir-ACTH in response to CRF administration in the HPD fetuses, which was qualitatively similar to that observed in sham-operated fetuses. In contrast, the plasma cortisol response was less in HPD fetuses when compared to that in sham-operated fetuses. The results of this study demonstrate that ir-ACTH secretion is not maintained by the fetal hypothalamus in the last third of gestation, and that ir-ACTH secretion is tonically inhibited by the hypothalamus during this time. The disconnection of the pituitary from the hypothalamus disrupts the maturation of the pituitary-adrenal axis, thus demonstrating the fundamental importance of the hypothalamo-pituitary axis in the normal maturational cascade which culminates in birth in this species.
Antolovich
G C
GC
Department of Anatomy, University of Melbourne, Parkville, Australia.
McMillen
I C
IC
Robinson
P M
PM
Silver
M
M
Young
I R
IR
Perry
R A
RA
D000311:Adrenal Glands / Q000196:embryology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000196:embryology* / Q000502:physiology / Q000601:surgery; D010902:Pituitary Gland / Q000196:embryology* / Q000502:physiology / Q000601:surgery; D011247:Pregnancy; D012756:Sheep
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone