Dehydroepiandrosterone Sulfate Secretion Research Articles

The effects of α-human atrial natriuretic polypeptide on steroidogenesis by fetal zone cells of the human fetal adrenal gland

The human fetal adrenal gland is primarily composed of fetal zone cells, which exhibit a high rate of steroidogenesis and a rapid growth rate during fetal life. α-Human atrial natriuretic polypeptide has been shown to inhibit basal and adrenocorticotropic hormone-stimulated steroidogenesis in the human adult and in some human adrenal adenoma cells. The purpose of this investigation was to determine the effect of atrial natriuretic polypeptide on steroidogenesis by fetal zone cells. Dispersed fetal zone cells were incubated in Krebs-Ringer's medium with adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate and in the presence of atrial natriuretic polypeptide. The medium was analyzed for content of dehydroepiandrosterone sulfate and cortisol by radioimmunoassay. The addition of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate increased the secretion of dehydroepiandrosterone sulfate and cortisol twofold to threefold and twofold to sixfold, respectively, above basal rates. Atrial natriuretic polypeptide significantly inhibited basal dehydroepiandrosterone sulfate and cortisol secretion. When cells were incubated in the presence of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate plus atrial natriuretic polypeptide, cortisol secretion was inhibited 50% to 90% and dehydroepiandrosterone sulfate was inhibited 25% to 50%. Atrial natriuretic polypeptide had no effect on the metabolism of progesterone tagged with carbon 14 in fetal zone cells. In conclusion, atrial natriuretic polypeptide inhibited basal and adrenocorticotropic hormone-stimulated steroid secretion by fetal zone cells. Furthermore, these results suggested that the action of atrial natriuretic polypeptide was by inhibition of cholesterol side-chain cleavage or transfer of cholesterol to the mitochondrion.

Effects of atrial natriuretic factor (ANF) on rat testicular steroidogenesis in vitro.

The aim of this study was to evaluate the effects of rat atrial-peptide type II (rAP-II) on testicular steroidogenesis by isolated adult rat Leydig cells. rAP-II stimulates testosterone secretion. The maximal stimulatory effects of rAP-II on testosterone production occurred at the dose of 10(-11) M. At the same dose this peptide stimulates androstenedione and dehydroepiandrosterone-sulphate production, two important testosterone precursors of delta-4 and delta-5 steroidogenetic pathways, respectively. At higher doses, 10(-9) and 10(-7) M, the stimulatory effect of rAP-II on testosterone secretion is strongly declined, on androstenedione secretion is abolished, whereas on dehydroepiandrosterone-sulphate secretion remains unaffected. These data suggest that rAP-II at low doses exerts a stimulatory effect on the early steroidogenetic step by isolated adult rat Leydig cells. At higher doses this peptide seems to influence the testicular steroidogenesis, probably exerting a limiting reaction step involving the 3-beta-OH-steroid-dehydrogenase activity.

The role of calmodulin antagonists on steroidogenesis by fetal zone cells of the human fetal adrenal gland.

The adrenal gland of the human fetus (HFA) is relatively large compared to that of the adult and exhibits an extremely high rate of steroidogenesis both in vivo and in vitro. The fetal zone cells make up 80-85% of the volume of the HFA and are the major site of steroid production during fetal development. We have recently demonstrated that calcium is involved in the regulation of steroidogenesis in fetal zone cells of the HFA. There is considerable evidence that many actions of calcium within cells are mediated by the calcium-binding protein calmodulin. The purpose of the present investigation was to determine if calmodulin also plays a role in HFA steroidogenesis. To investigate this possibility, the fetal zone was dissected from fetal adrenals of first and second trimester human abortuses. After collagenase digestion of the tissue, dispersed fetal zone cells were maintained in a Krebs-Ringers medium at 37 C for a 3-h incubation. Cells were incubated with and without ACTH (10(-8) M) in the presence of the calmodulin inhibitors trifluoperazine (TFP), chlorpromazine (CPZ), and calmidazolium (CAL) at concentrations of 5-100 microM. The media were assayed for contents of dehydroepiandrosterone sulfate (DS), cortisol (F), pregnenolone, and cAMP by RIA. The addition of ACTH stimulated F secretion 5- to 10-fold compared to that in control fetal zone cells. DS secretion increased up to 5-fold and pregnenolone about 2-fold in the presence of ACTH compared to values in control cells. ACTH also stimulated cAMP secretion by 10-fold compared to that in control cells. The addition of TFP, CPZ, and CAL significantly inhibited ACTH-stimulated DS, F, and pregnenolone secretion in a dose-related fashion to near-control levels. We observed that TFP, CPZ, and CAL inhibited cAMP accumulation as well as Bu2cAMP-stimulated steroid secretion. The metabolism of 22R-hydroxycholesterol to pregnenolone was inhibited by TFP and CPZ, but not by CAL. These studies suggest that calmodulin plays a role in regulating steroidogenesis in fetal zone cells of the HFA.

Dehydroepiandrosterone-Sulphate Secretion and State of Adrenal Function in the Rat

This study was undertaken to gain better insight into dehydroepiandrosterone-sulphate (DHEA-S) secretion in rats, which is necessary for the subsequent investigation of the influence of nutritional status on DHEA-S secretion in this species (published as part II). DHEA-S as well as corticosterone (11-OHCS) blood levels were found to be markedly lower in dexamethasone-treated than in untreated rats. After adrenocorticotropic hormone (ACTH) administration DHEA-S and 11-OHCS increased significantly. A similar rise was seen for DHEA-S in metyrapone-treated rats. At the same time these animals exhibited a drastic elevation of 11-desoxycorticosterone (11-DOC). Furthermore DHEA-S levels of rats pretreated with ACTH prior to metyrapone application significantly exceeded the DHEA-S values measured in animals only given metyrapone. However, the DHEA-S level did not change clearly in rats treated with either a single or multiple doses of hCG, although the concentrations of DHEA, androstenedione, and testosterone were markedly elevated in these animals. These findings suggest that DHEA-S in rats is secreted chiefly (or exclusively) by the adrenal gland. Since a stimulative effect of ACTH pretreatment on the secretory DHEA-S response to subsequent metyrapone stimulation could be demonstrated, we conclude that stress (ACTH administration) associated with a stimulation of adrenal gland activity provokes an increase in the secretory capacity for DHEA-S.

The role of calcium in steroidogenesis in fetal zone cells of the human fetal adrenal gland.

The human fetal adrenal gland is composed primarily of fetal zone (FZ) cells, which have a high rate of steroidogenesis. The purpose of this study was to examine the role of calcium in the regulation of steroidogenesis by FZ cells. Dispersed FZ cells were incubated in Krebs-Ringers medium at 37 C for 3 h in the presence of ACTH, (Bu)2cAMP, or forskolin in addition to various drugs. The medium contents of dehydroepiandrosterone sulfate (DS), cortisol (F), and cAMP were quantified by RIA. After the addition of ACTH (10(-10)-10(-5) M), DS and cAMP secretion increased. The addition of EGTA to the medium inhibited ACTH- and forskolin-stimulated DS, F, and cAMP secretion by 50% as well as (Bu)2cAMP-stimulated steroidogenesis. The addition of calcium (10(-5)-10(-2) M) had only a slight effect on the secretion of DS or F in the absence of ACTH or (Bu)2cAMP. In the presence of ACTH and (Bu)2cAMP, however, increasing amounts of calcium resulted in a 2- to 3-fold increase in the rates of DS and F secretion. The addition of either A23187, a calcium ionophore, or verapamil, a calcium channel blocker, inhibited ACTH-stimulated DS and F secretion by 90%. The rate of cAMP formation was greater after ACTH plus verapamil treatment than after ACTH treatment alone, whereas A23187 inhibited ACTH-stimulated cAMP secretion to basal levels. Both A23187 and verapamil inhibited ACTH- and cAMP-stimulated pregnenolone secretion. The metabolism of 22R-hydroxycholesterol to pregnenolone was inhibited by A23187 and verapamil. In conclusion, our results suggest that extracellular calcium is important for activation of the human adrenal FZ cell adenylate cyclase system, while intracellular calcium plays a multifaceted role in controlling steroid production.

Persistence of Fetal Zone Function in the Infant Rhesus Mondey Adrenal Gland*

Plasma dehydroepiandrosterone sulfate (DHAS) concentrations increase markedly in the rhesus monkey fetus at the end of gestation. A further increase occurs in the infant. To determine whether the changes in plasma concentration between the fetus and infant represent maintenance of DHAS production by the infant adrenal gland, we measured the t1/2, distribution volume (VD), MCR, and production rate of DHAS in the late gestation rhesus monkey fetus (129-155 days gestation; term is 165 days) and infant (14-42 days of age). A single bolus dose of [3H]DHAS was injected into five fetuses and four infants, and blood samples were collected serially from 5 min to 24 h after the injection. The amount of [3H]DHAS in the circulation was measured after solvolysis, extraction, and Celite chromatography. The concentration of DHAS in each sample was measured by RIA. DHAS was cleared significantly more rapidly in the fetus than in the infant [MCR in fetus, 2.4 +/- 0.4 (+/- SE); MCR in infant, 0.6 +/- 0.2 liters day-1 kg-1]. The t1/2 of DHAS was shorter in the fetus than in the infant (1.0 +/- 0.1 vs. 3.3 +/- 0.7 h). Absolute VD values were larger in the fetus than in the infant (231 +/- 29 and 143.8 +/- 11.6 ml kg-1); however, they were similar when the fetal VD was calculated including placental weight as a component of fetal weight. The production rate of DHAS, calculated as the product of MCR and integrated plasma DHAS concentration for the duration of the experiment, was not significantly different between the fetus and the infant (1.0 +/- 0.2 and 3.3 +/- 1.2 mg kg-1 day-1) in spite of the marked differences in plasma DHAS concentrations (445.8 +/- 103.8 ng ml-1 in the fetus and 5165 +/- 1296 ng ml-1 in the infant). These results indicate that the adrenal of the infant rhesus monkey continues to secrete DHAS at a rate at least as high as that in the late gestation fetus. Since the infant maintains DHAS production similar to that of the fetus in the absence of the placenta, a corollary of these studies is that the elevated DHAS secretion in the rhesus infant is independent of the placenta or the hormonal milieu of pregnancy. The maintenance of a functional fetal zone in the adrenal gland makes the rhesus infant a suitable model to use in studying the regulation of DHAS secretion and fetal zone morphology.

Ovine prolactin potentiates the action of adrenocorticotropic hormone on the secretion of dehydroepiandrosterone sulfate and dehydroepiandrosterone from cultured bovine adrenal cells.

To determine the direct effect of prolactin on adrenal androgen secretion, the daily secretions of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione and cortisol were determined in monolayer culture of bovine adrenal cells in the presence or absence of adrenocorticotropic hormone (ACTH) and/or prolactin. In the absence of ACTH ovine prolactin alone had no effect on steroid secretion during seven-day culture. Ovine prolactin, when administered in combination with ACTH, significantly potentiated the stimulatory effect of ACTH on DHEA-S and DHEA but not androstenedione secretion on the seventh day in culture. On the first day in culture prolactin showed no synergistic effect with ACTH on DHEA and DHEA-S secretion, although ACTH significantly increased DHEA and cortisol secretion. DHEA-S secretion increased as a function of prolactin concentration in the presence of ACTH. These results indicated that long-term treatment by ovine prolactin with ACTH caused the increase in adrenal androgen secretion from bovine adrenal cells. The site of action of prolactin was suggested to be the partial inhibition of adrenal 3 beta-hydroxysteroid dehydrogenase by the result of increases in DHEA-S and DHEA but not androstenedione secretion.

Mechanism of dissociation of cortisol and adrenal androgen secretion after removal of adrenocortical adenoma in patients with Cushing's syndrome.

We investigated the mechanism of dissociation of cortisol and dehydroepiandrosterone sulfate (DHEA-S) secretion by the adrenal glands after the removal of an adrenal gland containing an adrenocortical adenoma in a patient with Cushing's syndrome. After removal of the adrenocortical adenoma, the serum cortisol rapidly decreased from 24.6 +/- 6.4 micrograms/dl (mean +/- SD, n = 6) to 0.7 +/- 0.5 micrograms/dl. Serum DHEA-S levels were 15 +/- 14 micrograms/dl and 6 +/- 9 micrograms/dl before and after surgery, respectively, and significantly lower than the control values. Serum cortisol levels reverted to normal levels 1.5 to 3 years after the surgery. On the other hand, DHEA-S levels reverted to normal 5 to 7 years after the serum cortisol levels had normalized. Monolayer cultures of normal human adrenal cells obtained at adrenalectomy in patients with advanced breast cancer and atrophic adrenal cells adjacent to the adrenocortical adenoma in patients with Cushing's syndrome were used to study the mechanism of the dissociation of cortisol and DHEA-S secretion. ACTH caused significant increases in the productions of pregnenolone (P5), progesterone (P4), 17-hydroxypregnenolone (17-OH-P5), 17-hydroxyprogesterone (17-OH-P4), DHEA, DHEA-S, androstenedione (delta 4-A), and cortisol. The amounts of 17-OH-P5 and 17-OH-P4 produced by ACTH in atrophic adrenal cells were significantly greater than those in normal adrenal cells. The amounts of DHEA, DHEA-S and delta 4-A produced by ACTH in atrophic adrenal cells were significantly smaller than those of normal adrenal cells. The conversion rate of 17-OH-[3H]P5 to 17-OH-[3H]P4 and 11-deoxy-[3H] cortisol was higher in atrophic adrenal cells than in normal adrenal cells, but the conversion rate to [3H]DHEA, [3H]DHEA-S and [3H]delta 4-A was significantly lower in atrophic adrenal cells than in normal adrenal cells. These results suggest that the dissociation of cortisol from DHEA-S after the removal of adrenocortical adenoma is a probably due to diminished C17,20-lyase activity in the remaining atrophic adrenal gland.

Serum dehydroepiandrosterone sulfate in Cushing's syndrome.

Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were measured in patients with hyperadrenocorticism. When compared to normal subjects of corresponding age, serum DHEA-S levels were normal or elevated in 37 patients with Cushing's disease. In contrast, DHEA-S levels were significantly lower than those of normal subjects in all 28 patients with hyperadrenocorticism due to benign adrenocortical adenoma, suggesting that ACTH is the major determinant of DHEA-S secretion and that determination of serum DHEA-S concentrations is useful in the biochemical differential diagnosis of the etiology of Cushing's syndrome. In six patients with adrenocortical adenoma, the recovery of suppressed DHEA-S secretion after removal of the adrenal gland affected by a tumor was studied. Serum cortisol levels normalized by the end of the second year after unilateral adrenalectomy, while DHEA-S levels remained low for at least 2 succeeding yr. The results suggest that deficient ACTH secretion may result in a greater and longer lasting loss in the ability of the adrenal cortex to secrete androgens than in the ability to secrete cortisol.

Dissociation of cortisol and adrenal androgen secretion in the hypophysectomized, adrenocorticotropin-replaced chimpanzee.

We tested the hypothesis that adrenal androgen production is supported by a pituitary factor distinct from ACTH. Six adult male chimpanzees who had completed adrenal maturation (adrenarche) were castrated and either hypophysectomized or sham hypophysectomized. Hypophysectomized animals received synthetic ACTH-(1-24) and T4 to prevent adrenal insufficiency and hypothyroidism. Adrenal function was evaluated with a 3-h ACTH infusion before and 7, 21, 40, 120, and 180 days after hypophysectomy. Plasma cortisol (F), dehydroepiandrosterone (DHA), DHA sulfate (DHAS), and androstenedione (delta 4A) were measured at six time points during the ACTH infusions. The mean ratios of DHA to F, DHAS to F and delta 4A to F during ACTH infusion were calculated as indices of the relative activity of the androgen pathway compared to that of the cortisol pathway. The DHA to F ratio during ACTH infusion was 31% of the pretreatment level 40 days after hypophysectomy (P less than 0.01 compared to the sham-hypophysectomized controls). The DHAS to F ratio during ACTH infusion, which paralleled the DHA to F ratio, also fell significantly (P less than 0.025). Hypophysectomy did not alter the delta 4A to F ratio. None of the ratios was altered by sham hypophysectomy. MCRs for F and DHA, which were measured before and 180 days after hypophysectomy or sham hypophysectomy, did not change significantly. Additionally, plasma corticosteroid-binding globulin levels remained unchanged throughout the study for both groups of chimpanzees. Thus, the changes in the DHA to F ratio cannot be explained by alterations in the MCRs of DHA or F or in the plasma transport protein for F. These data suggest that ACTH maintained normal F and delta 4A secretion after hypophysectomy but failed to maintain normal DHA and DHAS secretion. This is consistent with the hypothesis that normal delta 5-adrenal androgen secretion is dependent upon a non-ACTH pituitary factor or with the hypothesis of different ACTH requirements for the maintenance of F and delta 5-adrenal androgen secretion.

Effect of angiotensin II on secretion of adrenal androgens.

To assess the effect of angiotensin II (A II) on the secretion of human adrenal androgens (AA), plasma dehydroepiandrosterone (DHEA), DHEA sulfate (DS) and delta 4-androstenedione (delta 4-A) were measured in eight normal men 60 and 120 min after stimulation of endogenous A II by a bolus injection of 40 mg frusemide, and the direct effect of A II on the secretion of adrenal androgens was examined in cultured human adrenocortical cells in the presence of a low concentration of ACTH. The administration of frusemide led to a significant increase in the plasma DHEA and DS concentration as well as plasma renin activity (PRA) and aldosterone concentration (PAC), but did not change plasma cortisol and delta 4-A. In the culture of human adrenocortical cells, 10(-9)-10(-5) M A II or 10(-13) M ACTH alone did not stimulate the secretion of DHEA, DS and delta 4-A, while 10(-7) and 10(-5) M A II in the presence of 10(-13) M ACTH caused a significant increase in DHEA and DS secretion with no change in delta 4-A. These results suggest that the activated renin-angiotensin system stimulates the secretion of adrenal androgens by a direct effect of A II on adrenal cortical cells.

A radioimmunoassay for dehydroepiandrosterone sulfate in the circulation of rhesus monkeys

A radioimmunoassay for dehydroepiandrosterone sulfate (DHAS) was established and validated for use in the rhesus monkey. The validation demonstrated the co-migration of immunoreactive material with tritiated dehydroepiandrosterone after hydrolysis and indicated the absence of other interfering steroids in the measurement. The application of this assay to perinatal samples verified that there are microgram quantities of DHAS present in the circulation. The measurement of circulating concentrations of DHAS in male and female rhesus monkeys at different stages of development demonstrated the absence of increases associated with puberty in this macaque species. Concentrations of DHAS were similar in adult males and females, but were elevated in pregnant females (p<0.05). Adult males had increased DHAS concentrations after GnRH administration (p<0.05), but no change was detected in infant male monkeys. Cortisol and DHAS responses of both infant and adult males occurred at a similar dose of ACTH (0.05 mU per kg versus 0.015 mU per kg, infant and adult, respectively). These data demonstrate the validity of the DHAS measurement in the rhesus monkey and suggest that the secretion of DHAS from infant and adult adrenals is generated by a similar stimulus. Since there was no evidence of gonadal secretion of DHAS in the infant, changes in either adrenal secretion and/or metabolic clearance of DHAS probably account for the microgram concentrations found during the perinatal period.

Enzymic synthesis of steroid sulfates XVI. Specificity and regulation of human adrenal hydroxysteroid sulfotransferase

Pure hydroxysteroid sulfotransferase (EC 2.8.2.2) of human adrenal glands possesses a wide substrate specificity towards steroids. This wide specificity has now been found to extend to simple alcohols; normal aliphatic alcohols from C 3 onwards acting as substrates with C 9 showing the highest rate. Increased rate was accompanied by a decrease in Km. In marked contrast to the sulfurylation of steroids such as dehydroepiandrosterone, which exhibit wave-like kinetics, the kinetics with simple alcohols were of the normal Michaelis-Menten type. By means of enzyme antibody and enzyme stability studies evidence was provided that one and the same enzyme was responsible for sulfurylation of hydroxyls on the 3- and 17- positions of steroids and simple alcohols. The data lend support to previous evidence that the enzyme controls the secretion of dehydroepiandrosterone sulfate via steroid-specific binding sites, enabling self-regulation in response to ACTH action.

Dehydroepiandrosterone sulfotransferase localization in human adrenal glands: a light and electron microscopic study.

Dehydroepiandrosterone sulfate is the major secretory product of the human adrenal cortex. The enzyme responsible for the sulfurylation, which has been isolated previously, possesses kinetic properties suggesting that it plays an important regulatory role in dehydroepiandrosterone sulfate secretion. In order to study the localization of the enzyme in the respective zones and cells of the cortex, an antibody to the pure enzyme was raised and the immunoglobulin G fraction employed in the peroxidase-antiperoxidase method. Staining was confined to the zona reticularis but was unevenly distributed throughout the cells. Electron microscopic examination of sections prepared from fresh adrenal tissue fixed in glutaraldehyde, revealed that the enzyme was predominantly clustered around lipid droplets. It is suggested that this may reflect an association of organelles, cholesterol being transported from lipid droplets to surrounding mitochondria, and pregnenolone then being converted to dehydroepiandrosterone in the adjacent endoplasmic reticulum and thence immediately sulfurylated.

Evidence for an influence of the ovary on circulating dehydroepiandrosterone sulfate levels.

Circulating dehydroepiandrosterone sulfate (DS) declines in old age, falling to almost undetectable levels after the seventh decade. Since an accelerated decrease occurs after the menopause, we sought to determine whether ovarian factors may influence adrenal DS secretion independent of chronological age. DS, cortisol, and estradiol levels were compared in subjects grouped according to age, ovarian function, and estrogen replacement. Our data show that premature ovarian failure and ovariectomy in young as well as in postmenopausal subjects precipitate an earlier decline in DS levels. There were no accompanying changes in cortisol levels and no correlations among levels of DS, cortisol, and estradiol. Long term estrogen replacement (over 10 yr) in postmenopausal women over age 65 had no beneficial effect on the age-related DS decline. We suggest that ovarian factors separate from estrogen-mediated effects significantly influence the reduction of DS levels independent of age.

Human Fetal Adrenal Cell Responses to ACTH and Pituitary Extracts

Human fetal adrenal tissues were studied in dispersed cell suspensions prepared by collagenase digestion;triplicate aliquots were incubated for 2 hours; control cells were compared to cells stimulated with 3 dilutions of ACTH and compared to responses from cells stimulated with 3 dilutions of 2 fractions prepared from human pituitaries (“A” and “B”). Crude fraction A contained FSH, LH and TSH; B contained ACTH, MSH and other peptides. 4 specimens with single adrenal weights of 128 mg, 243 mg, 488 mg and 915 mg were studied. Incubation medium was analyzed for dehydroepiandrosterone sulfate (DHAS) and corticoids (C). Unstimulated C secretion was similar in all weights (137 ± 63 pg/ml/100,000 cells); DHAS secretion was variable but increased with increasing size (16 ng/ml to 56 ng/ml/100,000 cells). ACTH caused dose-related proportionate increases in both DHAS and C in all; pit. frx “A” gave greater DHAS responses than ACTH in the 243 mg adrenal: DHAS:C ratio of 233:1 for ACTH and 7051:1 for “A.” However, this was not found in the more mature 915 mg gland (311:1 for ACTH and 191:1 for “A”). “B” reacted like ACTH. We conclude that (a) the developing fetal adrenal shows changing responses to different stimuli, perhaps reflecting changes in receptor response, number or discrimination, and (b) pituitary extract “A” may contain an androgen stimulator effective at variable stages of development.

Fetoplacental Steroid Metabolism in Prolonged Pregnancy and Postmaturity Syndrome

Previous work from this laboratory (Pediat. Res. 14:1367, 1980) showed that post-term infants (>42 wk. gestation) with postmaturity syndrome had normal umbilical venous dehydroepiandrosterone sulfate (DHAS) levels, but low unconjugated estriol (E3) levels, as compared to post-term infants with no evidence of dysmaturity. To investigate further whether placental conversion of neutral steroids to estrogens is more limiting for E3 production than fetal adrenal DHAS secretion, we studied 14 women with prolonged prognancy (>42 wk) and 9 control 39-41 wk gestation women by 50 mg I.V. DHAS infusions 1-3 days before delivery. The DHAS T½ was longer in post-term pregnancies than in controls (3.46 ± 1.13 hr vs. 2.79 ± 1.05 hr, p <0.01), and the estrone (E1) increases at 2 and 3 hr., and estradiol-17β (E2) increases at 2 and 4 hr. (p<0.05) were less in post-term than control pregnancies. These findings indicate diminished placental aromatizing function in prolonged pregnancy. However, no differences between pregnancies with and without post-mature fetuses could be found. In contrast, E1, E2 and DHAS levels in umbilical venous blood levels were similar, and E3 levels were lower (p<0.05), in postmature newborns when compared to controls. These cord blood values indicate that fetal hepatic 16α-hydroxylase may be the limiting step in fetoplacental E3 production in some postmature fetuses.

Gonadal and adrenal secretion of dehydroepiandrosterone sulfate in prepubertal and pubertal subjects

The Authors have evaluated the relationship between the secretion of dehydroepiandrosterone sulfate (DHA-S) by the adrenal glands and by the gonads in a group of prepubertal and pubertal subjects ("short normal"), both males and females. In the male subjects of a hCG test and an ACTH test were performed; in the female subjects only the latter test was carried out. The behavior of DHA-S under basal conditions was also assessed in both sexes and related to bone age and chronological age in the prepubertal period and during the early stages of puberty. Plasma levels of DHA-S in both sexes increase progressively with chronological age and bone age. A negative correlation was found between DHA-S and bone delay (expressed in percent relative to chronological age) in prepubertal subjects, both males and females. A significant increase in DHA-S after hCG stimulation was found both in prepubertal and pubertal boys. After ACTH stimulation DHA-S increased significantly in prepubertal and pubertal males and females; throughout the test no difference was found between prepubertal and pubertal subjects nor between male and female subjects. Our data confirm that DHA-S is produced both by the adrenals and by the testes.

Prolactin modulation of dehydroepiandrosterone sulfate secretion

To clarify the controversy about the effect of prolactin (PRL) on dehydroepiandrosterone sulfate (DHEA-S), this study was undertaken to investigate the effects of alterations in plasma PRL on plasma DHEA-S concentrations in hyperprolactinemic women, as well as in normal male subjects. DHEA-S was measured in a group of 21 women with hyperprolactinemia, galactorrhea, and amenorrhea (PRL: 257 ± 89 ng/ml; mean ± SEM). In these women, mean plasma concentrations of DHEA-S (2.54 ± 0.2 μg/ml) were significantly higher (p < 0.005) than those in 41 normal control women (1.78 ± 0.1 μg/ml) and those in a group of 11 amenorrheic patients (1.77 ± 0.2 μg/ml). Eight women with hyperprolactinemia were given 5 mg of bromocriptine each day for 4 consecutive weeks. Within 1 week of medication, PRL levels fell by 60% (p < 0.05). To test whether lowering normal plasma levels of PRL would affect plasma concentrations of DHEA-S, five normal male subjects received a 48-hour infusion of dopamine at an average rate of 6 μg/kg/min. Plasma levels of PRL fell by 60% (p < 0.01) after 8 hours of infusion, and DHEA-S decreased by 27% by 16 hours (p < 0.05). These data suggest that PRL modulates the secretion of DHEA-S: an increase in plasma levels of PRL is correlated with elevated concentrations of DHEA-S, whereas a decrease in PRL is followed by a fall in DHEA-S.

Plasma dehydroepiandrosterone sulphate in hypothyroid premenopausal women.

Plasma dehydroepiandrosterone sulphate (DHEAS), cortisol (F) and prolactin (PRL) were measured in seventeen premenopausal women with primary hypothyroidism and in fifteen normal premenopausal women. Significantly lower (P < 0.001) DHEAS levels were found in hypothyroid women while F and PRL were in the range of normal controls. No significant relation was found between DHEAS and total thyroxine (T4) and TSH. Our results support the hypothesis that DHEAS secretion is impaired in some women with primary hypothyroidism.