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PubMed1979

[Effect of 17-alpha-hydroxyprogesteronecapronate on sodium excretion and the renin-angiotensin-aldosterone-system in humans].

In seven healthy male subjects, a natriuretic effect of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHPC) was demonstrated. Three of these subjects were kept on an uncontrolled diet and were examined over a period of 12 days. To the remaining four subjects, a single dose of 250 mg 17 alpha-OHPC was given intramuscularly after four days of intake of a chemically defined diet (Vivasorb). In this second test procedure, blood samples were taken in the recumbent position every two hours throughout a period of 12 h after the injection. For two more days and during the days before the administration of 17 alpha-OHPC, blood was taken at 8 a.m. before getting up from bed in same intervals, urine was collected for analysis of sodium and potassium excretion. During the first 12 h after the injection of 17 alpha-OHPC, the urinary sodium/potassium ratio significantly increased in all subjects. Plasma renin activity showed no characteristic changes at this time, whereas the plasma concentrations of aldosterone and cortisol decreased. The decrease of cortisol concentration started immediately after the injection and was more pronounced than that of plasma aldosterone. During the following 36 h, renin activity as well as aldosterone and cortisol concentrations in plasma showed an increase; in contrast, the sodium/potassium ratio decreased. On the basis of these results, the following effects of 17 alpha-OHPC are discussed: (1) an acute natriuresis which may be due to a competitive inhibition of aldosterone at the renal tubules, and (2) an inhibition of pituitary ACTH secretion or of adrenal steroid biosynthesis.

Adult↗

PubMedDate not supplied

[Effect of chronic prostatitis on the endocrine activity of the testes].

It was shown in experiments on rabbits that androgenopoiesis was disturbed in the testes under conditions of aseptic chronic inflammation of the prostate: against the background of a sharp reduction of testosterone and androstendion formation there was observed production and discharge into the blood of great amounts of progesterone, this being not characteristic of the incretory activity of the intact gonads. It is suggested that the search for the ways of steroidogenesis restoration in the testes under conditions of induced pathology should be directed to the activation of enzymes catalyzing the processes of progesterone transformation into 17-alpha-hydroxyprogesteron, androstendion, and testosterone.

Androstenedione↗

PubMed1978

[In-vitro studies on the effect of D-norgestrel and norethisterone acetate on the formation of sex steroids in the human ovary].

In vitro incubations with slices of four normal human ovaries and 4-(14)C-pregnenolone as precursor were carried out to study the possibility of a direct influence of D-norgestrel and norethisterone acetate on the metabolism of pregnenolone. In agreement with our previous studies the in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, estrone and estradiol represents the characteristic profile of steroids of the ovaries from the corpus luteum phase. The in vitro-synthesis of 17 alpha-hydroxypregnenolone, DHA, androstenediol (basic metabolites) and androstenedione represents the characteristic profile of steroids of the ovaries from the follicle phase. The addition of D-norgestrel and norethisterone acetate to the incubation medium influences these steroid profiles in the same way. The metabolites of these characteristic profiles were inhibited by the progestogens, whereas the basic metabolites increased. In previous studies the same influence was found by addition of chlormadinone acetate. The influence of these progestagens on the two different profiles of steroids indicate that D-norgestrel and norethisterone acetate exert an inhibitory effect on the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase system and the aromatase system of the human ovary. These results suggest that these progestogens act directly upon ovarian function, an action which may be assumed to be operative in their contraceptive effect.

17-alpha-Hydroxypregnenolone↗

PubMed1992

Mild adrenal 3 beta-hydroxysteroid dehydrogenase deficiency in children with accelerated growth, premature pubarche and/or hirsutism.

We studied eight children (seven girls and one boy, of whom three are siblings) with accelerated growth, premature pubarche and/or hirsutism between the ages of 7 and 9.5 years. These patients were studied for the presence of adrenal steroidogenic defect by adrenocortico tropic hormone (ACTH) stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Baseline and stimulated 17-hydroxypregnenolone (delta 5-17P), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), androstenedione (delta 4-A), testosterone, and cortisol levels were measured. Six children, including three siblings, were diagnosed with a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency based upon the elevated response of serum delta 5-17P and the elevated ratio of delta 5-17P/17-OHP and of DHEA/delta 4-A to ACTH stimulation. Thus, a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency may not be uncommon in children with accelerated growth, premature pubarche and/or hirsutism and routine assay of delta 5-steroid metabolites should be generally available.

17-alpha-Hydroxypregnenolone↗

PubMed1992

Adrenal glands of mouse and rat do not synthesize androgens.

Human adrenal glands produce considerable amounts of the C-19 steroids dehydroepiandrosterone (DHEA) and androstenedione. To investigate the capability of rodent adrenals to produce these steroids, cell suspensions of mouse and rat adrenal glands were incubated in the absence and presence of adrenocorticotropic hormone (ACTH). Corticosterone levels in the incubation medium increased dramatically in the presence of ACTH, but no significant amounts of 17-hydroxyprogesterone or androstenedione could be detected. This indicates that the adrenals of rat and mouse lack the enzyme 17 alpha-hydroxylase. Absence of plasma cortisol in the presence of high levels of corticosterone confirmed these data. Plasma levels of androstenedione were significantly decreased in castrated male rats as compared to levels observed in intact males, showing the contribution of the testes to the plasma content of androstenedione. Very low levels of androstenedione were observed in female, male and castrated male mice. Plasma concentrations of DHEA were not detectable in intact and castrated male mice and rats. It is concluded that rat and mouse lack the enzyme necessary to synthesize adrenal C-19 steroids and that the adrenals in these animals, therefore, do not contribute to plasma levels of androstenedione and DHEA.

17-alpha-Hydroxyprogesterone↗

PubMed1978

Changes in peripheral hormone levels after therapeutic abortion.

Plasma levels of progesterone, 17 alpha-OH progesterone, hPL and beta-subunit hCG were measured in a group of women for 24 h after therapeutic abortion. Progesterone, hCG and hPL levels fell more rapidly than 17 alpha-OH progesterone levels. This might suggest that the main site of synthesis of 17 alpha-OH progesterone is probably in the corpus luteum of pregnancy or that the prolonged half-life of hCG maintains the corpus luteum to secrete longer. Human placental lactogen fell dramatically within 4 h but the hCG level was maintained. This difference probably reflects only the differences in half-lives of these hormones.

17-alpha-Hydroxyprogesterone↗

PubMed2026

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17α-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with ≥3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17α-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17α-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans↗

PubMed1992

Detection of functional ovarian hyperandrogenism in women with androgen excess.

BACKGROUND: Distinguishing between ovarian and adrenal causes of androgen excess may be difficult. We have found that women with the polycystic ovary syndrome have supranormal plasma 17-hydroxyprogesterone responses to the gonadotropin-releasing hormone agonist nafarelin. We determined the usefulness of testing with nafarelin to distinguish ovarian causes of hyperandrogenism in women. METHODS: We studied 40 consecutive women with hyperandrogenism who had oligomenorrhea, hirsutism, or acne. All 40 underwent testing with nafarelin, dexamethasone, and corticotropin with measurement of circulating concentrations of gonadotropins and steroid hormones, and 19 underwent ovarian ultrasonography. RESULTS: The plasma 17-hydroxyprogesterone response to nafarelin was supranormal in 23 of the 40 women (58 percent), and the plasma androgen response to corticotropin was elevated in 23; 13 women had both abnormalities. Only one woman had conclusive evidence of a steroidogenic block; she had nonclassic adrenal 21-hydroxylase deficiency. Of the 23 women with abnormal responses to nafarelin, only 11 (48 percent) had elevated base-line serum luteinizing hormone concentrations. Of the 13 women with abnormal responses to nafarelin who underwent ultrasonography, 7 (54 percent) had polycystic ovaries. Peak plasma 17-hydroxyprogesterone concentrations after nafarelin administration correlated closely with plasma free testosterone concentrations after dexamethasone administration (r = 0.75, P less than 0.001). CONCLUSIONS: Approximately half of women with oligomenorrhea, hirsutism, or acne have an abnormal response to the gonadotropin-releasing hormone agonist nafarelin, suggesting an ovarian cause of their androgen excess.

17-alpha-Hydroxyprogesterone↗

PubMed1992

The corticotrophin releasing factor test: a valuable and rapid procedure for the differential diagnosis of hirsutism.

Plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone, testosterone, delta 4-androstenedione and dehydroepiandrosterone sulphate were determined in 10 regularly menstruating hirsute women 0, 15, 30, 60, 90 and 120 min after intravenous injection of 100 micrograms corticotrophin releasing factor. The baseline concentrations of adrenocorticotrophic hormone, cortisol, progesterone and dehydroepiandrosterone sulphate were within the normal range, whereas the mean delta 4-androstenedione and testosterone concentrations were mildly elevated. The administration of corticotrophin releasing factor induced a rapid and significant increase in plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone and delta 4-androstenedione after 60 min, whereas dehydroepiandrosterone sulphate and testosterone concentrations were not significantly elevated. These findings suggest that the corticotrophin releasing factor test can readily be used as an out-patient procedure to exclude adrenal hirsutism.

17-alpha-Hydroxyprogesterone↗

PubMed1978

Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery.

In order to obtain the still lacking reference data of individual plasma steroids in the immediate postnatal period needed for the assessment of adrenocortical function in various neonatal maladaptation syndromes, aldosterone (A), corticosterone, deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone were simultaneously followed in the same human newborn in a single 250-500 microliters peripheral plasma sample obtained at constant times during the first week of life using a mechanized Sephadex LH-20 multicolumn chromatography and standardized RIAs. Mean concentrations in 12 spontaneously delivered full term newborns of either sex and in paired umbilical (UV) and peripheral maternal (MV) venous plasma are given in the table. Besides significant maternoumbilical gradients in each steroid, DOC, P, 17-OHP, and cortisone, originating predominantly from the fetoplacental unit, disappear rapidly with steadily increasing half-lives. A, corticosterone, and cortisol, however, remain elevated in comparison with later infancy, with the exception of a marked "glucocorticoid dip" in cortisol and corticosterone levels between 2 and 12 h after birth.

17-alpha-Hydroxyprogesterone↗

PubMed1978

Pituitary-adrenal axis activity in treated congenital adrenal hyperplasia: static and dynamic studies.

The pituitary-adrenal axis activity was evaluated in 43 patients, treated for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, by measuring plasma ACTH, 17-hydroxyprogesterone (17-OHP), testosterone, and aldosterone. Dynamic studies were performed by injecting 250 micrograms synthetic ACTH im and collecting blood samples 1 h later for steroid analysis. Twelve to fourteen hours after the last hydrocortisone dose given the evening before, plasma ACTH fluctuated widely from less than 10-475 pg/ml, 17-OHP exceeded normal values and varied from 1-275 ng/ml, while testosterone ranged from 3-151 ng/100 ml. The correlations between ACTH and 17-OHP (n equal 61, r equal 0.665, P less than 0.001) and between 17-OHP and testosterone (n = 43, r = 0.761, P less than 0.001) were good, while that between 17-OHP and aldosterone (n = 64, r = 0.512, P less than 0.001) was rather poor. One hour after ACTH injection, the mean level of 17-OHP was significantly increased as compared to the mean basal level [96.8 ng/ml +/- 10.6 (SE) as compared to 67.0 ng/ml +/- 8.1 (SE)]. However, only 12 out of the 48 tests showed a positive response equal to or greater than 100%, and the majority of these responses (10 out of 12) occurred when basal levels of 17-OHP were between 10-70 ng/ml. This suggests that when basal levels fall outside these values, the pituitary-adrenal axis is either too inhibited or too stimulated to react to exogenous ACTH. Of the 48 tests where 17-OHP was measured, 23 had basal level values within these limits, the mean being 40.3 ng/ml. The corresponding mean ACTH level was 99 pg/ml with a wide range (1-230 pg/ml). On the other hand, in prepubertal children who exhibited 17-OHP concentrations between 10-70 ng/ml, testosterone varied from 3-30 ng/100 ml, with a mean of 16.0 ng/100 ml +/- 1.9 (SE) which is not different from the mean level found in normal children [14.0 ng/100 ml +/- 1.3 (SE)]. Thus, under the influence of endogenous ACTH which is moderately increased, 17-OHP concentrations far exceed normal values, whereas plasma testosterone seems to be unaffected.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Pituitary-adrenal responses to corticotropin-releasing hormone in different degrees of adrenal 21-hydroxylase deficiency.

21-Hydroxylase congenital adrenal hyperplasia (21-OHCAH) involves a primary defect of the adrenal gland and a secondary involvement of ACTH secretion. The responses of the pituitary-adrenal axis to ovine CRH (oCRH, 1 micrograms/kg) were examined in subjects with different degrees of 21-OH deficiency. We studied 43 subjects: 7 classical and 6 nonclassical (NC) 21-OHCAH patients, 15 heterozygotes (HT) and 15 control subjects. Baseline plasma ACTH levels were higher in classical CAH than in NC-CAH, HT, and control subjects (mean +/- SEM, 66 +/- 14, 6 +/- 1.6, 4 +/- 0.5, and 5 +/- 0.5 pmol/L, respectively). The mean plasma ACTH response to oCRH in NC-CAH (17 +/- 3 pmol/L) was higher than in controls and HT (9 +/- 0.8 and 11 +/- 1.5 pmol/L). The highest ACTH responses to oCRH were obtained for classical CAH patients (126 +/- 29 pmol/L). Plasma cortisol rose after oCRH in control, HT, and NC-CAH patients but did not change in classical CAH. After oCRH, plasma 17-hydroxyprogesterone (17-OHP) were 4 +/- 0.5, 8 +/- 1.6, 93 +/- 28, and 359 +/- 110 nmol/L for controls, HT, NC-CAH, and classical patients, respectively. There was a significant correlation (r = 0.70) between 17-OHP and the ACTH responses to oCRH. The 17-OHP responses to oCRH were also correlated (r = 0.94) with the 17-OHP responses to the synthetic ACTH test. We conclude that the release of endogenous ACTH by oCRH result in graded 17-OHP responses on 21-OH deficiency. The present study also suggests that different degrees of adrenal biosynthetic defect may result in graded ACTH responses to oCRH.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Premature pubarche: etiological heterogeneity.

Premature pubarche is characterized by pubic hair, adult type body odor, acne, and axillary hair before 8 yr of age in girls and 9.5 yr of age in boys. Causes of this premature virilization include premature adrenarche, mild errors of steroidogenesis, precocious puberty, and adrenal and gonadal tumors. To determine whether any clinical parameters are helpful in distinguishing which children should undergo further evaluation for mild congenital adrenal hyperplasia, we performed ACTH stimulation tests in 69 children with premature pubarche and 8 pubertal controls. Patients were categorized as having typical (pubic hair with or without axillary hair and body odor) or atypical (pubic hair and genital enlargement) premature pubarche. Blood samples, before and 30 min after iv bolus administration of synthetic ACTH, were obtained for progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol measurements. The patients were divided into 4 groups based on their individual responses to ACTH stimulation: premature adrenarche (no apparent defect in steroidogenesis), possible decreased 21-hydroxylase activity, possible decreased 3 beta-hydroxysteroid dehydrogenase activity, and indeterminate responses. Five of 11 (45%) children with atypical premature pubarche and 7 of 58 (12%) children with typical premature pubarche were found to have evidence of mild defects in steroidogenesis. Similar to previous reports in postpubertal women, only responses to ACTH stimulation allowed accurate classification of these patients.

17-alpha-Hydroxypregnenolone↗

PubMed1992

The role of adrenocorticotropin testing in evaluating girls with premature adrenarche and hirsutism/oligomenorrhea.

To identify biochemical predictors for future development of hirsutism and/or oligomenorrhea (H/O) in girls with premature adrenarche (PA), we performed dexamethasone-suppressed ACTH stimulation tests in girls with PA (n = 46), young women (n = 44) with H/O, and adult women (n = 31). Cortisol, androstenedione, dehydroepiandrosterone, and 17-hydroxyprogesterone were measured. Seven girls with PA (15%) and seven with H/O (16%) had evidence of nonclassical adrenal steroid biosynthetic defects [nonclassical congenital adrenal hyperplasia (NCAH)]. Twenty-five girls with PA (54%) and 28 girls with H/O (64%) had the moderately elevated 17-hydroxyprogesterone response to ACTH that has been reported in obligate heterozygotes for 21-hydroxylase deficiency. There were no clinical features that distinguished the girls with NCAH from the others. ACTH testing is an important tool in distinguishing those girls with PA and H/O who have NCAH. Although we could find no differences in other adrenal steroid hormones that might predict which of the other girls with PA might late develop H/O, black girls comprised a substantially smaller fraction of the population with H/O than of the population with PA (2% vs. 26%; chi 2 = 8.5; P less than 0.005). This observation suggests that PA, in blacks who do not have NCAH, is more likely to be a benign condition/than in other ethnic groups.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency.

Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4-androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia.

Adrenal tumors are being detected more frequently in consequence of the wider application of increasingly sensitive radiological investigation techniques. According to the working hypothesis that more silent adenomas could develop from hyperplastic tissue areas under increased stimulation of the adrenal cortex, heterozygous and homozygous patients with congenital adrenal hyperplasia (CAH) were studied. A high incidence of adrenal masses, nearly 82% in homozygous and 45% in heterozygous patients, was found. There was no correlation between tumor size and serum 17-hydroxyprogesterone concentrations. These tumors are, therefore, probably silent adenomas. On the basis of these results, CAH should always be ruled out in the case of incidentally detected adrenal masses. Since CAH is a relatively frequent disease, and the adrenal carcinoma belongs to the rarest malignant tumors, a malignant transformation of these tumors seems to be unlikely.

17-alpha-Hydroxyprogesterone↗

PubMed1992

The newborn with ambiguous genitalia.

The unexpectedness of genital ambiguity in an infant creates an urgent and stressful situation. A logical approach, using a team of specialists together with nursery staff and physicians, allows each member to contribute expertise and unnecessary overlap of investigations. The psychological needs of the parents should be recognized, because their relation with the infant will determine the success of the assigned gender role in the future.

17-alpha-Hydroxyprogesterone↗

PubMedDate not supplied

Flutamide: a rational approach to hirsutism.

The Authors would show the effectiveness of flutamide, a potent selective antiandrogen, by an analysis of 30 patients with moderate to severe hirsutism. This therapy caused a marked improvement of clinic symptoms.

17-alpha-Hydroxyprogesterone↗