Mice with the recessively inherited obese-hyperglycemic syndrome (ob/ob) and their nonobese litter mates were studied over a 26-week period. The body weights and serum glucose levels of ob/ob mice began to rise markedly at 5-6 weeks of age and remained elevated throughout the period of study. Obese mice were significantly heavier (P less than .001) and had higher serum glucose levels (P less than .001) than lean mice, but obese mice had variably lower serum growth hormone (GH) and prolactin (PRL) levels (P less than .001) than lean litter mate controls after 4-5 weeks of life. A 24 h rhythm study performed on 15-week-old mice revealed a relatively unaltered but attenuated pattern of GH and PRL secretion in ob/ob mice. During and after the development of the obese-hyperglycemic syndrome, the low levels of these two hormones probably indicates an altered hypothalamic regulation of pituitary function.

A 76-year-old woman with virilization had menopausal levels of circulating LH and FSH, and a markedly elevated concentration of plasma testosterone (9130 pg/ml) into the range for adult men. Plasma cortisol and androstenedione levels andurinary 17-ketosteroid secretion were normal. Ethinyl estradiol suppressed plasma testosterone, LH, and FSH levels into the normal range for premenopausal women, but the testosterone concentration was unaffected by the administration of dexamethasone or ACTH. Retrograde venous sampling and angiography localized a right adrenal adenoma preoperatively. Following adrenalectomy, there was a prompt fall in testosterone, but there was no change in the LH concentration. Thus, this patient had an adrenal adenoma which secreted only testosterone and appeared to be gonadotropin-responsive. Testosterone levels in the adult male range failed to suppress gonadotropins. The significance of these findings is discussed.

Insulin responses to clinical grade human growth hormone (hGH), intact hGH, naturally occurring diabetogenic substance (NDS), and subtilisin cleaved forms of hGH (S1 and S3) were studied using hypophysectomized rat pancreatic islets. While clinical grade hGH (200 microgram/ml) elicited a prompt and sustained release of insulin, purified intact hGH (200 microgram/ml) did not. Naturally occurring diabetogenic substance, isolated from clinical grade hGH preparations, stimulated insulin release at 200 ng/ml. Upon repeat stimulation with NDS, a significantly greater insulin release than with initial stimulation was observed. Although S3 (200 microgram/ml) elicited significant insulin release, S1 (200 microgram/ml) did not. Direct stimulation of insulin release with clinical grade hGH is not due to intact hGH but another proteins(s) such as NDS. Enzymic modification of intact hGH appears to enhance insulin stimulatory capacity.