The factors that control adrenal steroid secretion and metabolism were investigated in rats made diabetic with Streptozotocin (65 mg/kg) and used one month after treatment. Diabetic animals possessed high resting levels of plasma corticosterone accompanied by adrenal hypertrophy; the showed an increased response to the stress of i.p. cold water injection. Moreover, the pituitaries of diabetic rats seemed to be releasing ACTH continuously and not storing it. Upon adrenal inhibition with Aminoglutethimide the expected increase in adrenal cholesterol and weight was of a smaller magnitude than in controls. The activity of liver enzymes that reduce ring A of corticosterone showed decreased activity in diabetics, which suggests that more corticosterone rather than its inactive metabolites were available to--but not able to suppress--the steroid feedback sites. The half-life of corticosterone in blood was similar in diabetes and controls. These results suggest that (a) diabetic animals were in a chronic stress condition; (b) the threshold for steroid feedback was less sensitive to variations in plasma corticosterone; (c) there is an abnormal peripheral disposal of corticosterone, but that other factors, besides the liver, regulate the clearance of the hormone from the circulation in the diabetic animals.

Male Wistar rats were treated with an i.v. dose of 100 mg/kg of Streptozotocin (STZ). Either 5 days or 1, 2 or 3 months after induction of diabetes, the adrenal function of these animals was studied. Short course diabetes (5 days) was accompanied by adrenal hypertrophy and high plasma corticosterone levels; during later periods the diabetic rats consistenly showed signs of adrenal hyperactivity, yet both adrenal weight and plasma corticosterone tended to be lower than in the 5 day-treated animals. Adrenal incubations with 14C-progesterone showed that 5 days and one month diabetic animals synthesized more deoxycorticosterone than controls; production of corticosterone and 18-hydroxydeoxycorticosterone was normal at all time periods studied. Synthesis of 18-hydroxycorticosterone, a compound which affects sodium metabolism, was increased in 5 day-treated rats; thereafter, the function of the zona glomerulosa seemed to be impaired in diabetic rats. These results suggest that early after induction of diabetes there is adrenal hyperfunction of the mixed type (i.e. gluco and mineralcorticoid), and that in the later periods (2-3 months), the deranged metabolism of the diabetic rat acts as a chronic stress.

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Subtotally pancreatectomized (95 %) white male rats do not show sexual disturbances during the prediabetic stage. During the stage of manifest diabetes, disturbances appear, and their severity increases progressively with the duration and degree of hyperglycemia. Fasting blood sugar levels from 120 mg% to 200 mg% are associated with disturbances of sexual behavior, with diminution of insemination capacity , and reduction or abolition of the biosynthesis of androgens in vitro. Blood sugar levels higher than 200 mg % are associated with an increase in the previous mentioned changes and lesions of the testicular tubules that can progress up to the complete abolition of the germinal epithelium. In summary, the sexual changes in the male 95 % pancreatectomized rat are related to the level of hyperglycemia. The mechanism is unknown.

The effect of streptozotocin diabetes on some ovarian functions in adult rats was examined. Diabetic diestrus animals showed reduced ovary weight and lower circulating levels of progesterone. Scatchard plots of binding data derived from ovarian particulate fractions of normal and streptozotocin diabetic rats revealed the presence of one class of binding sites with high affinity for '251-hCG. The apparent association constant of the hCG receptors of diabetic ovaries was comparable to that of normal gonads. However, a marked decrease (42%) in the number of hCG binding sites was found in diabetic animals. With isolated luteal cells similar results were obtained, and the administration of insulin to streptozotocin diabetic rats restored to normality the number of hCG binding sites. The maximal response of progesterone production by luteal cells from control ovaries was obtained with lo-'' M hCG. A 100-fold higher concentration of hCG was required for the maximum stimulation of cAMP synthesis. The cAMP response of cells from diabetic rats was significantly higher than that of control cells. However, luteal cells from diabetic rats showed some loss of sensitivity in the synthesis of progesterone during incubation with hCG. Most of the alterations seen in diabetic female rats could be restored with insulin therapy, indicating that insulin plays an important role in the regulation and maintenance of normal reproductive functions. It is suggested that the diminution of the LH receptor population causes the disruption of normal luteal cell function. This fact could be responsible for some of the reproductive alterations in the diabetic female rat.123