DHEA) And Its Sulfate Research Articles

Changes in steroid pattern following acute and chronic adrenocorticotropin administration in premature adrenarche

Biochemically adrenarche is characterized by increased production of 5-ene steroids, in particular Dehydroepiandrosterone (DHA) and its sulphate (DHA-S). It is still not clear if ACTH is responsible for this adrenal steroid production. The aim of the present study was to evaluate the effect of acute and chronic ACTH administration, without dexamethasone pretreatment, on hormonal patterns in 20 patients (5 males aged between 6 1 2 and 7 10 12 years and 15 females aged between 5 9 12 and 7 6 12 years) with idiopathic premature adrenarche. Pregnenolone (5P), DHA, DHA-S, 17-hydroxyprogesterone (17-OHP), androstenedione (A), 11-deoxycortisol (S) and Cortisol (F) have been determined by Radioimmunoassay. The results of the hormonal evaluation (means ± standard error) showed high plasma levels of DHA [329.2 ±41.7 ng/100 ml (dl)] and DHA-S (169.1 ± 54 μg/dl) and slightly increased levels of 5P (74.4 ± 7.1 ng/dl), of A (45.4 ± 4.6 ng/dl) and 17-OHP (69.3 ± 11.3 ng/dl) in comparison to those of controls, thus indicating a decrease in 3β-hydroxysteroid dehydrogenase activity and an increase in 17–20-lyase and 17-hydroxylase activities, characteristic for adrenarche. Acute and chronic ACTH stimulation did not amplify the characteristic basal hormonal pattern, but they induced a shift of adrenal steroid metabolism to 4-ene pathway, suggesting that the basal hormonal pattern in premature adrenarche may be independent or, at least, not exclusively dependent on ACTH control.

Lack of Adrenarche in Two Children with Precocious Puberty Secondary to Hypothalamic Hamartoma

Adrenarche, which occurs earlier than gonadarche in normal children, is marked by increases in plasma dehydroepiandrosterone and its sulfate (DHAS). Adrenarche and gonadarche can be dissociated in various situations, e.g. central precocious puberty, indicating that they are controlled by independent mechanisms. This report concerns 2 children with central precocious puberty secondary to hypothalamic hamartoma. Their plasma basal DHAS values, compared to other cases with central precocious puberty not secondary to hamartoma, remained low for chronological age and bone age over a follow-up of 6.3 (case 1) and 9.2 9.2 years (case 2): in case 1 (boy), DHAS was 9 micrograms/dl at chronological age 7.7 and bone age 13 years; in case 2 (girl), DHAS was 11 micrograms/dl for chronological age 10.5 and bone age 13.5 years. GH secretion was normal. Basal plasma cortisol levels as the levels during hypoglycemia and after corticotropin stimulation were all normal. These data suggest that hypothalamic hamartoma may affect the central control of adrenarche. They may also contribute to the diagnosis of hypothalamic hamartoma.

A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy

The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.

The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens in patients with advanced prostate cancer.

The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens was investigated in 6 patients with untreated advanced prostate cancer, aged 52-75 yr. Flutamide was administered (250 mg three times daily) for 10 days; before and after treatment, a synthetic ACTH1-24 stimulation test (250 micrograms im, with blood sampling immediately before and 60 min after the stimulus) was performed. Basal plasma 17OH-pregnenolone (delta 5-17OHP), 170H-progesterone (delta 4-17OHP), androstenedione (A), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) were unchanged by flutamide treatment. In contrast, basal plasma testosterone (T) concentrations significantly increased (p less than 0.05). The response of cortisol delta 4-17OHP, delta 5-17OHP, A and DHEA to ACTH, as well as the ACTH-stimulated delta 5-17OHP/delta 4-17OHP, delta 5-17OHP/DHEA, delta 4-17OHP/A and DHEA/A ratios, were unchanged by flutamide treatment. These findings indicate that: a) Short-term flutamide administration enhances testicular steroidogenesis, via augmented LH pulse frequency; b) Adrenal steroidogenesis seems to be not affected by the drug, since ACTH-stimulated plasma levels of adrenal androgens and precursors/products ratios were unchanged.

Dehydroepiandrosterone and its sulfate enhance memory retention in mice

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), major naturally occuring precursors of both androgenic and estrogenic steroids, were shown in the present study to have convincing memory enhancing effects in mice. Post-training intracerebroventricular (i.c.v.) administration of DHEA in dimethylsulfoxide (2 μl) prevented the amnesia for footshock active avoidance training (FAAT) caused by the same volume of dimethylsulfoxide alone. DHEAS significantly enhanced retention of FAAT in weekly trained mice whether injected i.c.v. or s.c. immediately post-training or given in the drinking water for a 2-week period. In the latter instance DHEAS was shown to facilitate retention of FAAT without enhancing acquisition. The maximally effective doses were: i.c.v., 162 ng/mouse; s.c., 700 μg/mouse; and oral, 1.45 mg/mouse/day. DHEAS administered i.c.v. occluded the amnestic effects of anisomycin (inhibitor of protein synthesis) and scopolamine (muscarinic cholinergic antagonist). There was a time-dependence of facilitatory effects of post-training i.c.v. administration of DHEAS on retention of FAAT, significant enhancement of retention being observed when it was given either immediately (within 2 min) or at 30 and 60 min after training, but not at 90 or 120 min. DHEAS given i.c.v. also improved retention for step-down passive avoidance. In all instances, those-dependent inverted U curves were obtained in a manner typical for memory enhancing substances. At a practical level, these experiments open new possibilities for the development of substances that may help in alleviating amnestic disorders in man.

Orchidectomy or oestrogen treatment in prostatic cancer: effects on serum levels of adrenal androgens and related steroids.

Peripheral serum levels of dehydroepiandrosterone (DHA) and its sulphate (DHAS), 4-androstene-3, 17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and albumin were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS. Dehydroepiandrosterone, cortisol and albumin were unaffected by treatment. Oestrogen treatment caused a pronounced decrease in the serum levels of DHA, DHAS, 17-OHP and A-4 and a small but significant decrease in serum albumin. Cortisol levels increased, probably due to elevated transcortin levels. The ratio of DHA to DHAS was unaffected by either orchidectomy or by oestrogen treatment. These results confirm that the testis contributes to circulating DHAS. The mechanism behind the more pronounced decrease in adrenal androgens during oestrogen treatment is not known but, for DHAS, increased metabolic clearance due to the decrease in albumin levels may contribute in this respect. The unchanged values for the ratio of DHA to DHAS indicate that this sex-specific sulphatase/sulphotransferase balance is insensitive to endocrine manipulations in adult men. The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy.

Adrenal function in infertile women

The influence of adrenal function on the menstrual cycle and infertility is still unclear. Therefore an ACTH stimulation test was routinely performed in 156 women with fertility problems who attended the Fertility Center of the Women’s Hospital in Heidelberg between 1 January 1986 and 30 June 1986. 46 of these patients served as controls (C) and fulfilled the following criteria: 25 to 35 years old, normal weight, no hirsutism, no acne, biphasic cycles, normal basal concentrations of FSH, LH, prolactin, TSH and TSH after 200 μg TRH, no medication, no chronic illness. 36 of them had had tubai ligation after previous uneventful pregnancies and desired refertilisation, while 10 of them had a check-up before heterologous insemination. 36 additional paid volunteers were chosen in the same manner. During days 2-5 of the menstrual cycle, ACTH testing was performed between 8 and 9 a.m. From an indwelling catheter three blood samples were drawn in 15-min-intervals and pooled for determination of the basal concentrations of 17-hydroxypregnenolone (170H-Preg), 17-hydroxyprogesterone (170HP), cortisol, 21-deoxycortisol (21-DF), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT). 60 and 120 min after an intravenous injection of 250 μg ACTH, additional blood samples were taken. All hormones were determined by radioimmunoassays, partly after Chromatographie separation. The Table gives the upper limit (95th percentile) of the basal and stimulated hormone concentrations in C(n = 82).

Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities

Ninety-five adolescents with menstrual irregularities persisting since menarche were studied and the data analyzed in relation to gynecologic age. In each year, in the premenstrual phase, luteinizing hormone (LH), testosterone (T), and androstenedione (delta 4A) values were higher than those of adults. Estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), progesterone (P), and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) gradually increased up to adult values correlating with gynecologic age. By ultrasound, nearly half the ovaries were multicystic and ovarian volume was greater than that of adults in each gynecologic year. When the data were classified as ovulatory or anovulatory, ovulation appeared to be a dynamic process characterized by ovaries similar to those of adults and by increasing hormonal levels correlated to gynecologic age. By contrast, in anovulatory cycles, mean T, delta 4A, and LH values were stable in each year and constantly higher than in ovulatory cycles and adult controls. These findings suggest that, despite persistent irregular cycles, some adolescents normalize all endocrine and ovarian parameters toward maturity, while subjects with persistent irregular anovulatory cycles maintain marked hyperandrogenism, increasingly high LH values, and enlarged multicystic ovaries.

Determination of dehydroepiandrosterone and dehydroepiandrosterone sulphate in blood and tissue. Studies of normal women and women with breast or endometrial cancer

Radioimmunoassay methods for measuring dehydroepiandrosterone (DHA) and its sulphate (DHAS) in human plasma and tissues were developed and validated. Plasma levels were measured in men, pre- and postmenopausal women, and patients with endometrial or breast cancer. In the patients, tissue concentrations were also measured. Plasma DHA levels fluctuated synchronously with cortisol, but DHAS levels were less labile, and reached maximum levels during the day and were lowest at night. No obvious pattern was seen in relation to the menstrual cycle. Both DHA and DHAS levels fell with age, but DHA levels reached a plateau at about 60 years. No significant effect of weight on plasma levels was found. Plasma levels in the cancer patients were not significantly different from age-matched controls either when single samples were compared, or when mean 24 h levels were used. Endometrial tissue levels of DHA fell with age, unlike DHAS. In breast tumour tissue, DHA, but not DHAS concentrations were higher than in normal breast tissue. A good correlation between plasma and tissue DHAS levels was found, and DHA levels were also correlated in plasma and tissue. The correlations between plasma and tissue were not observed in tumour tissue, which may be due to altered tissue metabolism.

Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women

In a study of the origin of estrogens in patients with breast cancer, the concentrations of estrogens and their androgen precursors, and aromatase and 17β-hydroxysteroid dehydrogenase (E 2DH) activities were determined in normal glandular and cancerous breast tissue. The correlation between tissue estrogens, precursor concentrations, enzyme activities and plasma levels and/or receptor status were calculated. In both normal glandular and carcinomatous breast tissue, the concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), 5 androstene-3β, 17β-diol (5-Adiol), estrone (E 1), estradiol (E 2) and progesterone (P) were significantly higher than plasma concentrations. While testosterone (T) concentrations were similar, dehydroepiandrosterone (DHCA) and estrone sulphate (E 1S) concentrations were lower in tissue than in plasma. In carcinomatous tissue androgen concentrations were lower, but estrogen concentrations were higher than in glandular breast tissue. Estradiol (E 2) concentration was positively correlated with the receptor concentration with the mean E 2 concentration corresponding to an estimated receptor occupancy of about 25%, probably sufficient for a submaximal biological response. Aromatase and E 2DH (E 2 → E 1) activities were observed in all breast cancer and glandular breast tissues, activities being higher in carcinoma than in glandular breast tissues; nevertheless, aromatase activity accounts probably only for a small fraction of tissue estrogen concentration. E 2DH, but not aromatase activity, was significantly higher in estrogen receptor positive than in estrogen receptor negative tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) concentration; the latter two steroids are non competitive inhibitors of E 2DH which inactivates E 2 to E 1. This effect of DHEA (S) may constitute a mechanism by which these androgens stimulate cancer growth and a rationale (besides suppression of estrogen precursors) for medical or surgical adrenalectomy in hormone sensitive metastatic mammary cancer. E 2DH activity might constitute an additional marker of hormone dependency of mammary cancer.

The effects of spironolactone on adrenal steroidogenesis in hirsute women

The effect of spironolactone on adrenal androgen and cortisol production was studied in six hirsute women. Hirsute women were evaluated before and 1 month after receiving 200 mg of spironolactone daily. Basal levels of serum androgens, 17-hydroxyprogesterone (17-OHP), cortisol (F), corticosteroid-binding globulin, and plasma adrenocorticotropic hormone (ACTH) were normal and did not change with therapy. The delta maximum (delta max) responses after dexamethasone suppression and ACTH administration of dehydroepiandrosterone (DHEA), androstenedione (delta 4A), 17-hydroxypregnenolone, and 17-OHP were similar in hirsute women and ovulatory control subjects. After spironolactone administration, the delta max DHEA response was unchanged, whereas the delta max delta 4A response was decreased (P less than 0.05). The delta max ratios of DHEA/delta 4A and 17-OHP/delta 4A were significantly increased after spironolactone in hirsute women, which suggested inhibitions of 3 beta-ol-dehydrogenase-isomerase and delta 4 17,20 desmolase activities. A significant reduction in delta max F occurred after spironolactone administration (P less than 0.05). Although baseline 11-desoxycortisol (S) and the plasma S/ACTH ratio were unaltered, the delta max S/F ratio increased after treatment (P less than 0.01), suggesting an inhibition of 11 beta-hydroxylase activity. Inhibition of adrenal androgen production occurs with spironolactone, but only serum levels of delta 4A are decreased, whereas DHEA and its sulfate (DHEA-S) levels remain unchanged.

The effect of hyperprolactinemia on the diurnal variation of adrenal androgens

Morning and evening plasma cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) were measured in ten women with hyperprolactinemia secondary to pituitary adenomas and in seven control subjects with cyclic menses and normal prolactin (PRL) levels. Plasma cortisol and DHEA-S levels were comparable in both groups. A diurnal variation for cortisol and DHEA was identified and comparable in both groups. These findings indicate that PRL may not be an important physiologic regulator of adrenal androgen secretion.

Peripheral hormone levels and the endometrial condition in postmenopausal women.

Thirteen postmenopausal women with benign endometrial changes including proliferative, secretory and polypous endometrium, endometrial hyperplasia and atypia (group I) and 13 randomly selected age-matched controls with normal atrophic endometrium (group II) were studied with respect to serum levels of dehydroepiandrosterone (DHA) and its sulfate (DHAS), testosterone, total estrone, estradiol-17 beta, progesterone, FSH and prolactin. Serum levels of DHA, DHAS, testosterone and total estrone were significantly higher in group I than in group II; otherwise no significant differences were found. Mean values for body weight and for Broca's index, respectively, were almost identical in the two groups. It is speculated that the adrenal androgens may affect the endometrium in two ways, viz. via peripheral conversion to estrogens and/or via direct interaction with endometrial steroid receptors. The results give further support to the hypothesis of an association between adrenocortical hyperactivity and endometrial abnormalities including endometrial carcinoma.

Androgens and prolactin levels in hirsute women with either polycystic ovaries or “borderline ovaries”

The purpose of this study was to investigate the hypothesis that elevated serum prolactin (PRL) levels might explain the adrenal hyperandrogenism which is often associated with the ovarian hyperandrogenism in hirsute women. Accordingly, serum levels of estrone (E 1 ), estradiol (E 2 ), 17-hydroxyprogesterone (17-OHP), testosterone (T), dihydrotestosterone (DHT), androstenedione (∆ 4 A), dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), as well as serum PRL, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and their responses to thyrotropin-releasing hormone (TRH) and LH-releasing hormone (LH-RH) were assayed in 23 hirsute women, 16 with polycystic ovaries (PCO group) and 7 with “borderline ovaries” (BO group: ovaries with a normal appearance at laparoscopy but with histologic abnormalities similar to those of polycystic ovaries). The results were compared with those of 11 normal control subjects. Slightly elevated PRL levels (18 to 32 ng/ml) were found in ten hirsute women. Mean basal concentrations of PRL and LH, mean LH response, and mean concentrations of all the steroids except E 2 were significantly elevated in the PCO group. Most of these elevated hormone levels were present but less pronounced in the BO group. PRL response to TRH was normal in the hirsute women. We found no significant relationship between PRL and steroid hormone values. On the other hand, mean DHEAS, DHEA, and ∆ 4 A concentrations were higher in the group of the ten hirsute women with slightly elevated PRL concentrations than in the group with normal concentrations, but the difference was not significant. Thus, serum PRL is often slightly elevated in hirsute women with ovarian hyperandrogenism, although our data do not clearly support the hypothesis that these elevated concentrations induce the associated adrenal hyperandrogenism.

The effects of estrogen on adrenal androgens in oophorectomized women

The serum levels of adrenal androgens (aa) are lower in oophorectomized (OO) than in ovulating (OV) women. This study was carried out in an effort to further investigate these findings and to study the effects of administration of estrogen on the levels of aa in OO women. Ten OO and seven OV women participated in this study in which aa were measured basally and after stimulation with adrenocorticotropic hormone (ACTH), both before and 4 weeks after conjugated estrogens (CE). Seven women received 0.625 mg of CE, and five received 2.5 mg of CE. Compared to OV women, OO women had significantly lower levels of androstenedione (Adione), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), testosterone (T), delta 5-androstenediol (Adiol), and 17 beta-estradiol (E2) (p less than 0.01). In response to ACTH, OO women had smaller responses to Adione (p less than 0.05), DHEA (p less than 0.005), DHEA-S (p less than 0.01), 17-OH progesterone (17 Prog) (p less than 0.01), and 17-OH pregnenolone (17 Preg) (p less than 0.1). Furthermore, after ACTH, the ratio of 17 Prog/Adione was significantly higher in OO women (p less than 0.01), thus suggesting reduced 17,20-demolase (17,20D?) activity. Similarly, OO women had higher ratios of 127 Preg/17 Prog (p less than 0.1), DHEA/Adione (p less than 0.01), and Adiol/T (p less than 0.01), thereby suggesting reduced 3 beta ol dehydrogenase-isomerase (3 beta ol) activity. In response to CE, there was a dose-related increase in aa and cortisol. After 2.5 mg of CE, aa were significantly higher and similar to those levels in OV women. despite the known increases in sex hormone binding globulin-finding capacity and transcortin after estrogen, unbound T increased slightly, as did urinary free cortisol in women treated with 2.5 mg of CE. After treatment with estrogen, there was a dose-related change in the ACTH-stimulated steroid ratios that indicated and increase in 17,20D and 2 beta ol activities. In women who were gien 2.5 mg of CE, these enzyme activities were similar to those in OV women.

Chemiluminescence enzyme immunoassay of dehydroepiandrosterone and its sulfate using peroxidase as label

We report a highly sensitive enzyme immunoassay for dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) using horseradish peroxidase as the label enzyme. Separation of free and bound DHEA-peroxidase conjugate was by insolubilized antibody, prepared by coupling purified IgG of goat anti-rabbit IgG serum with Sepharose 4B or a polystyrene tube. The enzyme activity was measured by the chemiluminescence reaction using luminol and hydrogen peroxide as substrate. The faint chemiluminescence was measured by a photon counter. The sensitivity was 25 pg/assay tube for DHEA and 100 pg/assay tube for DHEA-S. Upon comparison, results obtained by radioimmunoassay and this method showed good agreement; r = 0.86 for free DHEA, r = 0.92 for acid-hydrolyzed DHEA-S and r = 0.91 for solvolyzed DHEA-S. The present method is applicable in the routine determination of DHEA and DHEA-S in biological fluid.

Testicular and adrenal androgens and their binding to plasma proteins in the perinatal period: Developmental patterns of plasma testosterone, 4-androstenedione, dehydroepiandrosterone and its sulfate in premature and small for date infants as compared with that of full-term infants

The patterns of the plasma concentrations of testosterone (T), 4-androstenedionc (Δ 4), dehydroepiandrosterone (DHA) and its sulfate (DHAS) and of Cortisol (F) observed during the first year of life in 96 premature (group I), 23 small for date (group 2) were compared to those of 430 full-term infants (group 3). The per cent of T and DHA bound to plasma proteins was measured by equilibrium dialysis and the unbound levels of T and DHA determined. In group 3, testicular activity, high at birth, declined by the first week of life parallel to the clearance of hCG, and reincreased thereafter. In males, peak levels of T were observed at 15–60 days of life: from 3 to 6 months T decreased correlatively with time. The triphasic pattern of T observed during the first month of life was similar in the three groups. However, in premature infants (group 1). the post-natal testicular activation lasted significantly longer than in group 3 while, in group 2. the temporal decline in T levels was intermediate between those observed in groups 1 and 3. The pattern of T was comparable among the females of the three groups. In group 3, adrenal androgens, high at birth, decreased progressively throughout the first year of life in a like manner in both sexes. In contrast in group 1, DHA and DHAS remained at comparable high levels for the first two months of life, then declined in both sexes, but DHA and DHAS were significantly higher in females than in males until 3 months of age. In group 2 adrenal production of androgens. both in level and duration, was again intermediate of that seen in groups I and 3. Plasma F levels did not differ between groups. The plasma binding of T and DHA increased both within the first month postnatally to prepubertal values with no sex difference and similarly in the three groups. It is hypothetized that maturational processes of the interrelationships of the components of both the hypothalamo-hypophyseal-testicular axis and the hypothalamo-hypophyscal-adrenal axis are related to a similar ontogenic evolution.

Sequential hormonal changes and activation of the hypothalamic-pituitary-gonadal axis

Plasma dehydroepiandrosterone (DHA) and its sulfate (DHAS), androstenedione (Δ), 17α-hydroxypro-gesterone (17-OHP), testosterone (T), oestradiol (E 2) and LH were measured in cord plasma and in plasma samples obtained in normal infants and children 3–18 months and/or 3.5–16 yrs of age. DHAS, Δ, 17-OHP, and T were elevated in cord plasma and decreased to relatively constant levels by 3 months except for T in male infants which was higher at 3 months than in cord plasma. LH was also higher at 3 months in male infants than later up to 18 months. A significant rise in DHA and Δ'was noted in girls between 6–8 and 8–10 years of age respectively while these hormones increased 1–2 years later in boys, prior to any significant rise in T and E 2. These studies confirm the reported activity of the hypothalamic-pituitary gonadal axis in early infancy together with the prepubertal adrenal activity leading to gonadotrophin release. Studies in the young lamb showed higher plasma LH and T values at 4–5 weeks and pulsatile release of LH, T and prolactin which were more important at 1 week and 8 weeks than at 4 weeks of age. in vivo and in vitro responsiveness to HCG was also more important at 1 week while the number of binding sites was identical. A complete dissociation between cAMP and T response to HCG was observed. It is suggested that the newborn lamb may be used as a model for the study of hypothalamic-pituitary gonadal relationships in man.

PROLACTIN AND ADRENAL ANDROGEN SECRETION

The aim of this study was to investigate the role of prolactin in the secretion by the adrenal of dehydroepiandrosterone (DHA) and its sulphate (DHA‐S). Therefore prolactin and DHA‐S levels were determined in different groups of subjects under various physiological and pathological conditions. In patients with prolactinomas, or with pharmacologically induced hyperprolactinaemia, plasma DHA‐S and, to lesser extend, DHA concentrations were elevated, and the DHA‐S blood production rate greatly increased. ACTH stimulation which did not influence DHA‐S concentrations in normals, caused a significant increase in patients with prolactinomas; the increase in DHA concentrations was similar in normal subjects and in prolactinoma patients. Bromocriptine treatment of prolactinaemia patients normalized both prolactin and DHA‐S concentrations. Acute elevation of prolactin in normal subjects by TRH stimulation or by short term administration of sulpiride, in contrast to long term treatment, did not influence DHA‐S levels. During pregnancy, notwithstanding high prolactin concentrations, DHA‐S concentrations were lower than during the menstrual cycle. In patients with prolactinomas, given glucocorticoid replacement with cortisol, DHA‐S concentrations were low (normal) notwithstanding persistently high prolactin concentrations. It is concluded that only prolonged elevation of prolactin induces increased DHA‐S secretion by the adrenal cortex and that normal ACTH secretion is a prerequisite for this effect. The absence of elevated DHA‐S concentrations in pregnancy might be explained by the rapid rate of metabolism, as the DHA‐S production rate is increased. The intimate mechanism of prolactin and ACTH interaction at the adrenal cortex remains however unknown.

Serum levels of testicular and adrenal steroids after dexamethasone adn HCG-administration in the laboratory-maintained Rhesus monkey.

ABSTRACT In order to evaluate the endocrine testicular and adrenal function of rhesus monkeys in vivo, and to compare this with the human situation, the effect of dexamethasone (Dxm), HCG and combined Dxm/HCG administration on the steroid levels was investigated in 8 adult male rhesus monkeys in November/December (= season of high testicular activity). Serum levels of cortisol, testosterone (T), androstenedione (A), 17-hydroxyprogesterone (17-OHP), oestradiol (Oe2), dehydroepiandrosterone (DHA) and its sulphate (DHA-S) were measured radioimmunologically. Basal T and DHA serum levels were similar to those found in man, whilst A levels amounted to 1/10 and DHA-S to 1/30 of human values. Oe2 and 17-OHP levels were higher than in man. T and A levels were not suppressed by Dxm and very high degrees of stimulation were reached after HCG. The HCG-induced increment in T was smaller under Dxm/HCG than under HCG alone. 17-OHP levels were reduced to 25% of basal levels under Dxm, but the incremental response to Dxm/HCG was the same as that without Dxm. DHA and DHA-S were 60 and 75% lower under Dxm, and the increment in DHA after Dxm/HCG was less than that after HCG. DHA-S did not respond to HCG. In conclusion, several important differences in basal steroid levels and in the response to dynamic testing were found in the rhesus monkey, as compared to man. The adrenal contributes 75% to circulating 17-OHP levels, and 60 and 75% respectively to DHA and DHA-S levels. A is produced solely by the testis in the rhesus monkey. As compared to man, the rhesus monkey testis in vivo synthesises T via both the Δ4 and Δ5 pathways. The Δ5 pathway appears to be dependent on adrenal steroid precursors.