Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one, I) sulfate (Ia) has been characterized in the anterior and the posterior parts of the brain of adult male rats. Its level (1.58 +/- 0.14 and 4.89 +/- 1.06 ng/g, mean +/- SD, in anterior and posterior brain, respectively) largely exceeded that of I in brain (0.42 +/- 0.10 and 0.12 +/- 0.03 ng/g in anterior and posterior brain, respectively) and of Ia in plasma (0.26 +/- 0.13 ng/ml). Brain Ia level did not seem to depend on adrenal secretion; it was unchanged after administration of corticotropin or dexamethasone for 3 days, and no meaningful change occurred in brain 15 days after adrenalectomy plus orchiectomy, compared with sham-operated controls. In contrast, stress conditions prevailing 2 days after adrenalectomy plus orchiectomy or after the corresponding sham operation resulted in a significantly increased concentration of Ia in the brain. Changes of Ia level in brain occurred irrespective of changes in corresponding plasma samples. It is proposed that Ia formation or accumulation (or both) in the rat brain depends on in situ mechanisms unrelated to the peripheral endocrine gland system.

Characterization and measurement of dehydroepiandrosterone sulfate in rat brain.

I. Introduction The human adrenal cortex secretes a variety of androgens, as shown in Fig. 1, in addition to cortisol and aldosterone. Some of these steroids function as androgens, or serve as precursors for androgen or estrogen formation in peripheral tissues. The control of glucocorticoid and mineralocorticoid secretion is largely under the influence of ACTH and the renin-angiotensin system, respectively. However, the mechanism of control of adrenal androgen (AA) secretion is less well defined, and is the main subject of this review. II. ACTH, Dexamethasone and AAs ACTH is the most widely accepted modulator of AA secretion at present. Rosenfield et al. (1) studied endogenous cortisol and dehydroepiandrosterone (DHA) secretion in a normal volunteer and found a correlation between the rhythmicity of secretion of cortisol and DHA, although the magnitude of the DHA rhythm was much less than that of cortisol. Other investigators have administered bovine ACTH or synthetic forms such as the peptide-(l–24) cosy...

Control of Adrenal Androgen Secretion

The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.

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Estradiol and Testosterone Secretion by Human, Simian, and Canine Testes, in Males with Hypogonadism and in Male Pseudohermaphrodites with the Feminizing Testes Syndrome

The Leydig cells, responsible for testicular androgen production, have two growth phases during the life-span of mammals. The fetal population appears during fetal life and is responsible for the androgen-induced differentiation of the male genitalia. The fetal Leydig cells disappear after birth, and the other population, the adult Leydig cells, appears during puberty and persists for the whole adult life. The fetal Leydig cells, evidently due to the intrauterine endocrine milieu and their special functional requirements in genital differentiation, differ both morphologically and functionally from the adult population. The purpose of this review is to elucidate the special features of the mammalian fetal Leydig cell population, which presents an intriguing experimental model for studies of function and regulation of steroidogenic cells.

Fetal Leydig cells: cellular origin, morphology, life span, and special functional features.

Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities.

Free and sulfate-conjugated neutral steroids in human testis tissue.

Blood samples were obtained from the spermatic and peripheral veins of 8 males during an operation for inguinal hernia. Three of the subjects were treated with human chorionic gonadotropin (HCG) before collection of the samples. Neutral steroids in the fractions of free, mono- and disulfated compounds were identified and quantified, using gas-liquid chromatography and gas chromatography-mass spectrometry. In addition to testosterone, androstenedione and dehydroepiandrosterone, the following unconjugated neutral steroids were found to be secreted by the normal human testis: 5-androstene-3β,17α-diol, 5-androstene-3β,17β-diol, pregnenolone, 17α-hydroxypregnenolone and 17α-hydroxyprogesterone. In subjects treated with HCG, the concentrations of all these steroids in spermatic vein plasma were considerably higher than in untreated subjects. In addition, considerable amounts of monosulfated pregnenolone, dehydroepiandrosterone and 5-androstene-3β,17β-diol were found to be secreted by the testis in thes...

Secretion of free and sulfate-conjugated neutral steroids by the human testis. Effect of administration of human chorionic gonadotropin.

The monosulfates of testosterone, androsterone, epiandrosterone, dehydroepiandrosterone, androst-5-ene-3β,17β-diol, pregnenolone, pregn-5-ene-3β,20α-diol, and pregn-5-ene-3β,17α,20α-triol and the disulfates of androst-5-ene-3β,17β-diol and pregn-5-ene-3β,20α-diol in the spermatic vein and peripheral blood plasma were quantified. The results show that, in normal subjects, testosterone sulfate, pregnenolone sulfate and possibly androst-5-ene-3β,17β-diol monosulfate are secreted by testis tissue.

E. A. Laitinen

Papers

Free and sulfate-conjugated neutral steroids in human testis tissue.

Secretion of free and sulfate-conjugated neutral steroids by the human testis. Effect of administration of human chorionic gonadotropin.

Secretion of neutral steroid sulfates by the human testis.