Adrenal steroidogenesis in the spontaneously hypertensive rat (SHR).

Adrenal vein catheterizations were done in SHR and control rats at different ages during the development of hypertension. All SHR became hypertensive by 15 weeks of age. The secretion rate of aldosterone was significantly reduced at 8 weeks of age, 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) at 12 weeks of age, deoxycorticosterone (DOC) at twenty weeks of age, and corticosterone (B) at 12 and 20 weeks of age. Secretion data suggest either an enzyme block, or increased conversion of known steroids to an unknown steroid product. Reduced secretion of corticosterone could explain the adrenal hyperplasia observed in SHR which may be important to the development of hypertension in these animals.

Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats.

Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance.

The control of steroidogenesis by human fetal adrenal cells in tissue culture. II. Comparison of morphology and steroid production in cells of the fetal and definitive zones.

Preparations of dispersed human fetal adrenal cells from the inner third of the gland and from the subcapsular area were maintained in culture, and their ultrastructure and steroid production were studied. The former type of preparation contained only fetal zone cells, while the latter contained definitive zone cells together with varying numbers of fetal zone cells. Both types could be cultured with equal ease, but during short term culture, fetal and definitive zone cells became morphologically indistinguishable. The patterns of steroid production and, in particular, the relative production of delta 4,3-ketosteroids and delta 5,3 beta-hydroxysteroids were similar in both preparations, as were their dose-response relationships during incubation with alpha ACTH-(1-24). Although considerable variability in total steroid production was observed between cells from different adrenal glands, in no specimen was any evidence for functional zonation of the fetal adrenal cortex observed in vitro. The results suggest that the apparently unique histological appearance and function of the fetal adrenal cortex may only reflect intense stimulation by ACTH secondary to the combined influences of a rapid cortisol MCR and of some inhibitor of fetal adrenal 3 beta-hydroxysteroid dehydrogenase activity.

Pathogenesis of hypertension in Cushing's syndrome.

Steroid production, plasma renin activity (PRA) and plasma renin substrate (PRS) were measured in eight patients with hypertension due to Cushing's syndrome of benign origin. Despite elevation of cortisol secretion in all patients, hypokalemia and suppressed PRA was noted in the one subject with a functioning adrenal adenoma. PRA was normal in six patients on an unrestricted sodium intake but was markedly increased in the two patients on low salt diets. PRS was significantly increased during active disease, but decreased substantially with treatment. The absence of uniform hypokalemia and of suppression of renin indicates that mineralocorticoid production could not account for the increase in arterial pressure. It is suggested that glucocorticoid-induced hypertension may be initiated by alterations in vascular responsiveness to pressor agents and that elevated PRS levels may contribute to increase angiotensin formation.

Phenolic 9,10-secosteroids as products of the catabolism of bile acids by a Pseudomonas sp.

The obligate aerobe, Pseudomonas putida ATCC 31752, efficiently utilises bile acids as a source of carbon and energy for growth and maintenance. When aeration is considerably restricted, a consequence to the catabolism of the bile acids in a fermentor is an accumulation of certain steroidal catabolites. Evidence is presented to show that among these are hydroxy-9,10-seco-1,3,5 (10)-androstratriene-9, 17-diones and those from four of the common bile acids, cholic, chenodeoxycholic, hyodeoxycholic and deoxycholic acids have been isolated and their structures determined. The product of catabolism of hyodeoxycholic acid appears to exist in a hemi-acetal form which readily forms an acetal during isolation procedures. All but one of these are described for the first time.

Influence of age on the formation of 5alpha-androstanediol and 7alpha-hydroxy-testosterone by incubated rat testes.

Testes from rats of different ages were indubated with or without tritiated testosterone. The exogenously-added or endogenously-produced testosterone is mainly metabolized to 7alpha-hydroxylated testosterone in adult animals, and to 5alpha-reduced metabolites (especially 5alpha-androstanediol) in immature animals.