Effects of treatment with adrenocorticotrophin on the hypothalamo-pituitary-adrenal system.
Long-term treatment with adrenocorticotrophin (ACTH) inhibited the stress-induced response of the hypophysial-adrenocortical system 24 h after the final ACTH injection. The mechanism of this phenomenon was studied in both normal and adrenalectomized rats, the latter receiving corticosterone at various doses. The effect of electrical stimulation of the medial basal hypothalamus on the concentration of corticosterone in plasma (an indicator of ACTH secretion), the corticotrophin releasing factor (CRF) content of the stalk median eminence (SME), the ACTH content of the pituitary gland and the in-vitro release of ACTH by the pituitary gland incubated with or without addition of SME extract were investigated. Electrical stimulation of the medial basal hypothalamus failed to induce a rise in concentrations of corticosterone in plasma of normal rats treated with ACTH; moreover the levels of hypothalamic CRF and hypophysial ACTH were significantly decreased. Hemipituitary glands of ACTH-treated rats released markedly less ACTH in vitro in response to SME extract than did the control glands. This indicated that long-term hormone administration caused a serious impairment of the responsiveness of the corticotrophic cells toward CRF. Pituitary ACTH content and in-vitro responsiveness of pituitary glands obtained from ACTH-treated, adrenalectomized rats receiving corticosterone replacement seemed to be dependent on the amount of exogenous corticosteroid, but not on that of exogenous ACTH. Our previous and present findings suggest that long-term treatment with ACTH elicits repeatedly increased secretion of endogenous corticosterone, impairing the stress-induced CRF-ACTH release at both the hypothalamic and hypophysial levels. Our data challenge the view that ACTH itself is able to inhibit its own secretion.
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004558:Electric Stimulation; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone