Stress and ACTH increase circulating concentrations of 3 alpha-androstanediol in female rats

The present experiments were carried out to determine what physiological conditions are responsible for the acute increases in serum levels of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol, 3 alpha-Adiol) which are seen in the intact estrous female rat within 15-30 min after mating. Blood samples were obtained from proestrus rats immediately before and 20 min after injection of exogenous hormones or initiation of stress procedures, and plasma concentrations of 3 alpha-Adiol and/or progesterone (P) were measured in these samples by RIA. Intravenous injections of ovine LH (5, 15, or 45 micrograms) or saline resulted in equivalent significant increases in plasma 3 alpha-Adiol 20 min after injection. In contrast, dose-dependent increases in 3 alpha-Adiol were seen after intravenous injection of 0 (acidic saline vehicle), 2, 4, or 8 ng ACTH1-24 to dexamethasone-pretreated rats. The highest ACTH1-24 dose also resulted in a significant increase in plasma P concentration. In a third experiment, a significant increase in 3 alpha-Adiol concentration above baseline was seen at 20 min after onset of restraint stress; in this case plasma P concentrations did not increase significantly. Finally, blood samples were obtained after onset of ether/jugular venipuncture stress two days after ovariectomy (ovx), adrenalectomy (adx), or ovx+adx on diestrus. The plasma 3 alpha-Adiol response to stress was normal in intact sham-operated and non-operated groups of controls, but was significantly diminished in the ovx and the adx groups to 28.4% of that shown by the intact animals. Circulating 3 alpha-Adiol concentrations were undetectable in 22/26 samples obtained in the ovx+adx group. These data demonstrate that plasma concentrations of 3 alpha-Adiol increase in response to stress or ACTH but not LH, and that both the ovary and the adrenal contribute to this increase.