Androgen metabolism by rat epididymis. 8 Age dependent changes in androgen metabolizing enzymes in rat accessory sex organs.

The effect of age on in vivo tritiated testosterone (3H-T) metabolism and on epididymal 5 alpha-reductase and 3 alpha/beta-hydroxysteroid dehydrogenase activity has been studied on male Wistar rats. Following i.m. injection of 3H-T to 3 and 25 month old functionally hepatectomized rats, the accumulation of 5 alpha-androstan-17 beta-ol-3-one (DHT) by both the caput and cauda epididymidis, prostate, and seminal vesicles was significantly higher in the younger animals than in the old. The total conversion of 3H-T by both epididymal segments was unaltered with advancing age whereas a significant decrease was observed in both prostate and seminal vesicles. The ratio between 17 beta-hydroxy and 17-keto metabolites in the prostate and epididymis of both hepatectomized and intact animals decreased significantly with age. The ratio values for the seminal vesicles showed no significant age variation. The formation of total 5 alpha-reduced metabolites by epididymal homogenates showed a linear decrease with advancing age. The activity of 5 alpha-reductase fell from 16.1 to 10.3 ng/mg protein/30 min. 3 alpha/beta-hydroxysteroid dehydrogenase activity was unaffected by age. The reduced levels of active testosterone metabolites reported with old age are a result of a decrease in 5 alpha-reductase activity, the ultimate cause of which is most probably an age associated defect in the hypothalamic-pituitary-testicular feedback system.

Calcium and phosphate metabolism in acromegaly.

A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism. When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion. Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased. Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100 ml of glomerulus filtrate. It is concluded that parathyroid hyperactivity is a feature of acromegaly.

Evidence for androgen-dependent phosphodiesterase activity in rat seminal vesicle and epididymis.

This paper deals with findings implying the existence of an androgen-dependent phosphodiesterase (PDE) activity in accessory sexual glands (seminal vesicle and epididymis) of the rat. It is suggested that the PDE activity is not a prerequisite for, but merely a modulator of the overall androgenic response.

Recurrent and persistent Cushing's syndrome after assumed total bilateral adrenalectomy.

Two cases of recurrent Cushing's syndrome after assumed total bilateral adrenalectomy are presented. Both cases were due to adrenal tissue left at the adrenalectomy. In the first case the lack of preoperative localization of the adrenal remnant caused severe postoperative complications. In the other patient localization of the adrenal tissue was achieved by scanning after administration of 131I-19-iodocholesterol. The reoperation was easy and the postoperative course smooth.

Bromocriptine treatment in acromegaly: clinical and biochemical effects.

Eight selected patients with active acromegaly and elevated GH levels without other endocrine disturbances were submitted to long-term treatment and acute dose-response trials with bromocriptine. Seven patients showed clinical improvement and lowering of GH levels in response to long-term treatment, however, two of these showed only minor changes in GH levels during the acute dose-response trial. Glucose tolerance and heel pad thickness remained unchanged, while urinary hydroxyproline excretion and blood, plasma and erythrocyte volumes decreased. Using daily doses of 20 mg bromocriptine, side effects were generally minor. Severe vasovagal reactions were, however, observed in two patients, in one at the start of treatment, in the other after ingestion of 25 mg bromocriptine. Bromocriptine represents a valuable treatment alternative in acromegaly, but only long-term treatment will separate responders from nonresponders.

Metabolism of testosterone in the human prostate and seminal vesicles.

Tissue from the normal, hyperplastic and the cancerous human prostate as well as tissue from the human seminal vesicles are capable of metabolizing testosterone in vitro. By incubating minced tissue with 3H-testosterone for 2 hours at 37 degrees C the following radioactive metabolites were identified: testosterone (17 beta-hydroxyl-4-androsten-3-one), androstenedione (4-androstene-3,17-dione), androstanedione (5alpha-androstane-3,17-dione), 5alpha-dihydrostestosterone (17 beta-hydroxy-5alpha-androstane-3-one, DHT), 3alpha-androstanediol (5alpha-androstane-3alpha,17beta-diol), 3beta-androstanediol (5alpha-androstane-3beta-17beta-diol) and androsterone (3alpha-hydroxy-5alpha-androstane-17-one). When normal human prostatic tissue was incubated with 3H-testosterone approximately 40% of the hormone was metabolized and 30-35% of the metabolites were identified as DHT. There were apparently no differences in testosterone metabolism between the dorsal and lateral prostatic lobes. A much lower conversion of 3H-testosterone was observed in the seminal vesicles (24%). The same metabolites were formed by prostatic carcinoma tissue, although distinctive quantitative differences from the normal prostate were observed. Thus, only 23% of the testosterone was metabolized by cancerous tissue of which 15% was present as DHT. The formation of 17-keto metabolites and androstanediols in the prostatic carcinoma tissue was approximately the same as in the normal prostatic tissue. The most extensive metabolism of testosterone was found by incubation of tissue from benign nodular prostatic hyperplasia. About 65% of the testosterone was metabolized, and 40% of the metabolites were identified as DHT. Hyperplastic prostatic tissue also showed a significantly higher formation of 5alpha-androstanedoils and the other tissues examined. The high formation of DHT and 5alpha-androstanediols in benign nodular prostatic hyperplasia in comparison with normal and cancerous prostatic tissue and seminal vesicle tissue might indicate that these metabolites should be studied more closely as possible aetiological factors for prostatic hyperplasia. The very low metabolism of testosterone in prostatic carcinoma tissue should be examined further in relation to tumour differentiation and clinical effect of endocrine therapy.