Site of Action of Vasopressin in Causing Corticotropin Release1

Abstract

The corticotropin-releasing properties of lysine vasopressin and that of a porcine pituitary extract were compared by means of injections into hypothalamic sites or into the adenohypophysis of dexamethasone-pretreated rats of both sexes. In all cases the doses used for central injections were below the minimal dose capable of causing an increase in adrenal secretion of corticosterone after intravenous injection, so that corticotropin (ACTH-like) effects or contamination by ACTH could be excluded as a cause of increased adrenal secretion of corticosterone after the central injections. Vasopressin provoked extensive release of ACTH when it was placed in the median eminence of the hypothalamus, as did the pituitary extract. When the 2 substances were tested by intra-adenohypophysial injection, the vasopressin caused much less ACTH release and the extract caused more ACTH release than observed after intrahypothalamic injections. Morphine abolished the ACTH release after vasopressin injections at either site, as well as after the injection of the extract into the median eminence. However, morphine failed to abolish, or even diminish extensively, the ACTH release observed after injection of the extract into the anterior pituitary. From these results it was concluded that the extract contained activity resembling that of a corticotropin-releasing factor, but that vasopressin did not have such activity at the doses used. The vasopressin apparently acted directly on the hypothalamus to cause release of endogenous corticotropin-releasing factor. (Endocrinology 79: 328, 1966)

Hypothalamo‐pituitary‐adrenocortical function in rats with inherited diabetes insipidus.

“…Our finding that hypothalami from Brattleboro rats are capable of secreting considerable amounts of CRF in vitro, in response to trophic stimuli, does not support the recent proposal (Gillies & Lowry, 1979) that vasopressin is identical with the corticotrophin releasing hormone and that it requires a synergistic factor to express its full biological activity. However, our results do not preclude the possibilities that vasopressin may either stimulate the release of CRF (Hedge, Yates, Marcus & Yates, 1966) or potentiate the action of CRF at the pituitary level (Yates et al 1971). Of these the latter is more feasible for, although vasopressin has no effect on the secretion of CRF by isolated hypothalami in vitro (Burden, Harrison, Hillhouse, Ironmonger & Jones, 1975), minute concentrations of vasopressin (Buckingham & Leach, 1979) and vasopressin related peptides (Buckingham & van Wimersma Greidanus, unpublished observations) potentiate the corticotrophin releasing activity of hypothalamic extracts.…”

Diurnal Variation of Corticotropin-Releasing Activity in the Rat Hypothalamus

“…Even if this be the case, the possible maximal dose to be injected by our intrapituitary microinjection method would at best amount to approximately 4mU, as calculated back from the data of McCann and Haberland (1959) and Konig and Meyer (1967). As already reported (Hedge et al, 1966;Hiroshige et al, 1968a), this amount of vasopressin as well as oxytocin, when placed directly into the adenohypophysis, was proved quite ineffective in eliciting ACTH release. As to the biogenic amines present in the hypothalamus, daily rhythms were observed in the norepinephrine content of the rat hypothalamus (Manshardt and Wurtman, 1968) and also in the noradrenaline and histamine content in the caudate nucleus and mid-brain of the rat (Friedman and Walker, 1968).…”

Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor.

“…This discrepancy could be due to different routes of administration, species differences in rates of metabolism, or species differences in pituitary responsiveness to these hormones. Another explanation is that AVP might cause release of endogenous CRF in addition to having a direct action on the pituitary (30). The subjects in the present study had no signs or symptoms of stress after AVP injection, so a nonspecific stress response appears to be an unlikely explanation for their IR-ACTH and IR-cortisol responses to AVP.…”