Mechanism of Action of Estrogens on Insulin Content of the Rat's Pancreas. ∗

Abstract

Discussion and Conclusions

The finding of an increase in pancreatic insulin produced by prolonged estrinization of normal rats has been confirmed. It appeared possible that this effect might be mediated by the pituitary which in such estrinized rats is greatly enlarged. A stimulation of production and secretion by the pituitary of greater than usual amounts of a'pancreatrophic hormone' might account for the observed facts. The pancreatropic potency of the pituitaries of such estrinized rats was therefore tested, in comparison with that of untreated animals. No pancreatrophic action was evident upon implantation of 9 pituitaries of control rats. ∥ The same number of pituitaries of treated rats caused a slight increase in pancreatic insulin content, which by itself, cannot be regarded as sufficient evidence for the increased pancreatrophic potency of the glands. The hypothesis that the effect of the estrogen is mediated by the pituitary is, however, supported by the outcome of the second experiment, i. e., the failure to produce pancreatrophic effects in hypophysectomized rats with the same estrogen treatment which had marked effect in normal rats. That this failure was not due to the pronounced toxic action of the estrogen in such rats was demonstrated by its lack of effect also in rats receiving pituitary substitution therapy besides the implanted estrogen.

It is also noteworthy that estrinization does not lead to increases in liver weights or liver glycogen storage in hypophysectomized rats, as reported for normal rats. 4 It would thus appear very probable that the effect of estrogens on pancreatic insulin content as well as on liver weight and glycogen is mediated by the pituitary gland. Evidence will be discussed elsewhere 8 which indicates that the lactogenic hormone exerts a pancreatic insulin increasing action in normal and hypophysectomized rats. The recent finding 5 , 6 that the lactogenic hormone content of and excretion by the pituitary appears to be increased in estrinized rats stands thus in good agreement with the reported observations of an increased'pancreatrophic' function of the pituitaries of estrinized rats.

Summary. Two types of evidence favor the assumption that the activity of estrogens in elevating the pancreatic insulin content is mediated by the pituitary. (1) The pituitaries of estrinized rats when implanted elevate the pancreatic insulin content of the host animals while the pituitaries of untreated rats do not show this activity. (2) Estrogen which raises pancreatic insulin content in normal rats does not produce this effect in hypophysectomized rats.