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Gonadotropin-like substance in the preimplanted rabbit blastocyst.

The presence of a gonadotropin-like substance in preimplanted rabbit blastocyst fluid was determined bu radioreceptorassay of human chorionic gonadotropin (hCG)/luteinizing hormone (LH), using receptors prepared from bovine corpus luteum, rat testis, and rat ovaries. An average of 16.6 microliter of fluid containing 0.83 ng of luteotropic material was recovered from each blastocyst. An intense fluorescence was exhibited by the trophoblastic cells of the blastocysts treated with fluorescein-conjugated gamma-globulin isolated from antiserum raised against human chorionic gonadotropin. Serum concentrations of LH as well as estradiol, progesterone, and 17 alpha-hydroxyprogesterone up to day 6 after mating were determined in pregnant rabbits and compared with those in pseudopregnant and normal rabbits. In pregnant rabbits after mating, a surge of 62 +/- 15 ng of luteinizing hormone and 73 +/- 22 ng of progesterone/ml of serum occurred which returned to basal levels at 6 hours and on day 1, respectively. Secondary increases in serum luteinizing hormone of 26 +/- 12 to 36 +/- 16 ng/ml on days 3 and 5 and in serum progesterone of 16 +/- 4 and 14 +/- 5 ng/ml on days 5 and 6, respectively, were observed in pregnant rabbits.

Animals↗

The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia.

The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH.

Adrenocortical Hyperfunction↗

Steroid metabolism in vitro by gonadal tissue from a true hermaphrodite.

The case of a true hermaphrodite, with a normal ovary and an ovotestis is presented. The ovotestis was removed and incubated in vitro with tritiated steroids (testosterone, dehydroepiandrosterone, pregnenolone and 17 alpha-hydroxyprogesterone). Labeled metabolites were isolated and identified. Based upon these findings, a pathway of steroid biogenesis in this abnormal gonadal tissue is suggested. The ovotestis studied did not contain all the enzymes involved in ovarian steroidogenesis: 3 beta-hydroxysteroid dehydrogenase, isomerase, 17--20 desmolase and 17 beta-hydroxysteroid dehydrogenase were present, but other important enzymes, such as 16 and 17-hydroxylases, and aromatizing enzyme systems, were deficient or absent.

Dehydroepiandrosterone↗

Bilateral testicular tumors in congenital adrenal hyperplasia.

A 22-year-old male with bilateral testicular tumors and the 21-hydroxylase variety of congenital adrenal hyperplasia (CAH) was studied. Preoperatively, on his usual glucocorticoid regimen, his urinary pregnanetriol excretion was increased (8.0-23.5 mg/day), serum LH and FSH were normal to increased (14.3-28.7 mIU/ml and 13.2-19.5 mIU/ml, respectively) and testosterone (T) was normal to decreased (176-600 ng/dl). At surgery, testicular vein concentrations of 17-alpha-hydroxyprogesterone (17-OHP) and adnrostenedione (delta) were increased (30.1 mug/dl and 38.3 mug/dl respectively) while T was decreased (1,503 ng/dl); a positive peripheral vein--testicular vein gradient was not seen for these steroids. Following injection of 10 U of crystalline ACTH into the testicular artery; testicular vein concentrations of 17-OHP, delta and T increased to 729 mug/dl, 2,390 mug/dl and 9,660 ng/dl respectively. Microscopic examination of the testes revealed multinodular tumors composed of polygonal or rounded eosinophilic cells, arranged in cords, nests and clusters. The tumors extended from the hilus and compressed the adjacent testicular tissue. Electron microscopic examination of the tumors showed features, common to steroid-secreting tissues, with abundant smooth endoplasmic reticulum in close proximity to mitochondria which was moderate in number. The adjacent testicular tissue was composed of immature tubules with normally developed Leydig cells in the interstitial tissues. From these data and a survey of previous works, it was postulated that these tumors were dependent upon ACTH for growth and steroid secretion. In view of the high serum LH concentration seen in association with incomplete suppression of adrenal steroid secretion in this study and the association of evidence of gonadotropin secretion with testicular tumors in other CAH patients, LH may also have contributed to the growth of these tumors.

17-Ketosteroids↗

Approach to the mechanism of androgen overproduction in a case of Krukenbery tumor responsible for virilization during pregnancy.

Virilization may occur during pregnancy as the result of an ovarian Krukenberg tumor. mechanism of the androgen overproduction in this exceptional condition is still poorly understood. A new case is reported in which only in the postpartum clinical, endocrine, and endoscopic studies led to the diagnosis of an ovarian Krukenberg tumor secondary to a gastric carcinoma. In the mother, basal hormonal studies were done 1 and 4 weeks after delivery, then after gastric and ovarian surgery. Three months after delivery, ovarian steroid response to hCG (priming dose, 5000 IU; then 1500 IU every other day for 12 days) and a study of progesterone (P) metabolism at a steady state after a constant infusion of [3H]P and cold P (92 micrograms/min leads to blood production rate (BPR) of 152 mg/day designed to reproduce the BPR of P usually seen in pregnancy) were successively performed. Hormones were measured by specific RIAs after chromatographical purification. Basal hormonal levels were normal in the child. In the mother, on the 5th day postpartum, mean hormone levels (in nanograms per dl) were: testosterone (T), 4181; androstenedione (delta 4), 8876; 17 alpha-hydroxyprogesterone (17-OHP), 9746; P 1075; estrone (E1), 195; and estradiol (E2), 151. One month later, levels were normal for the follicular phase; T, 40; delta 4, 146; P, 52; E2, 9; and E2, 4.5. At both times, dehydroepiandrosterone was normal (703-750). Hormone levels increased progressively during hCG stimulation but their time course was different between hormones. At the end of the test, T. 144; delta 4, 746;' 17-OHP, 789; P, 723; E1, 37; and E2, 20. The MCR of P was decreased, 1450 liters/day (normal, 2020). Conversion ratios between products and precursor during constant infusion were normal. From these data, obtained in four different conditions (postpartum period, hCG stimulation, progesterone infusion, and after oophorectomy), the following can be concluded: adrenal production of dehydroepiandrosterone was normal; the ovarian overproduction of androgens likely resulted from the excessive reductive metabolism of both placental and ovarian P along the delta 4 steroid biosynthetic pathway by an hypertrophic stromal compartment; and HCG stimulation seems to be the necessary stimulus for this condition. The enhancement by T on its own peripheral production is also discussed.

Androgens↗

Adrenal suppression with aminoglutethimide. III. Comparison of plasma delta 4- and delta 5-steroids in postmenopausal women treated for breast carcinoma.

A regimen or aminoglutethimide in combination with replacement glucocorticoid has been used to suppress adrenal steroidogenesis in postmenopausal women with metastatic breast carcinoma. During acute and chronic treatment with aminoglutethimide, the levels of the delta 4-steroids [progesterone (P), 17 alpha-hydroxyprogesterone (17-delta 4-P), and androstenedione (delta 4-A)] and the delta 5-steroids [dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and 17 alpha-hydroxypregnenolone (17-delta 5-P)] were determine. In the total group of women, the plasma levels of P and delta 4-A increased 2- to 3-fold (P less than 0.05) while 17-delta 4-P rose 10-fold (P less than 0.01) from basal concentrations of 0.65 +/- 0.07 to 6.48 +/- 1.46 ng/ml during the initial 2 weeks of therapy with aminoglutethimide (AG) and dexamethasone. These three steroids then fell to basal levels during chronic treatment (P and 17-delta 4-P) or were suppressed (delta 4-A; P less than 0.001). In contrast, the levels of delta 5-steroids (17-delta 5-P, DHEA, and DHEA-S) were reduced 3- to 5-fold during the initial 2 weeks of therapy and remained suppressed throughout. The relative levels of certain delta 5- and delta 4-steroids pairs were then examined. The ratio of 17-delta 5-P to 17-delta 4-P decreased from baseline values of 2.15 +/- 0.35 to 0.38 +/- 0.21 ng/ml (P less .02) with the initiation of therapy and remained low thereafter. A similar pattern for the ratios between DHEA and delta 4-A, and DHEA-S and delta 4-A was observed. This may indicate that the regimen of AG treatment utilized may facilitate the activity of the 3 beta-ol-dehydrogenase, delta 5- to delta 4-isomerase, and accelerate the conversion of delta 5- to delta 4-steroids. The patterns of suppression of the plasma delta 4- and delta 5-steroids in oophorectomized and spontaneously postmenopausal patients with intact ovaries were analyzed separately. The plasma levels of progesterone were higher during the first 2 weeks of therapy in surgically castrate women than in spontaneously postmenopausal women (0.72 +/- 0.25 vs. 0.47 +/- 0.20 ng/ml). A similar pattern was observed for 17-delta 4-P, DHEA, and DHEA-S indicating that the adrenals might contribute to this increase. In contrast, during chronic treatment the levels of all steroids were lower in surgically castrate women than in those with intact ovaries. This suggested residual ovarian steroid during AG administration.

17-alpha-Hydroxypregnenolone↗

Lipid metabolic studies in oophorectomized women. Effects of three different progestogens.

Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks "wash out" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquid-chromatography. Both norethisterone and norgestrel caused a decrease in alpha-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway 1 for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From the present data it is suggested that the 19-norethisterone derivatives, norethisterone and especially norgestrel, have androgen-like influences on lipid metabolism. Medroxyprogesterone, being a 17-alpha-hydroxyprogesterone, caused less changes and consequently less disturbance of lipid metabolism.

Adult↗

Cutaneous hydroxystereoid dehydrogenases and rat-hair cycle.

The histochemical activity pattern of a number of hydroxysteroid dehydrogenases was studied during a provoked hair cycle in the rat skin. The intensity of reaction was high with dehydroepiandrosterone, estradiol, androsterone and pregnenolone, and none with 11-beta-hydroxyprogesterone, testosterone, dihydrotestosterone, 17-alpha-hydroxypregnenolone and 17-alpha-hydroxyprogesterone. Reactivity also varied with the hair cycle. The reactive sit-s were the acini of sebaceous glands and the hair sheaths.

17-alpha-Hydroxypregnenolone↗

Peripheral, ovarian, and adrenal vein steroids in hirsute women: acute effects of human chorionic gonadotropin and adrenocorticotrophic hormone.

In an attempt to localize the source of excessive andogens in hirsute women, various steroids were determined in peripheral blood, left ovarian venous blood, and left adrenal venous blood, using radioimmunoassay techniques developed in our laboratory. Peripheral serum levels of dehydroepiandrosterone, androstenedione, 5alpha-dihydrotestosterone, testosterone, progesterone, and 17 alpha-hydroxyprogesterone were elevated in several hirsute patients, compared with those of a group of normal, cycling women of the same age. There was direct evidence to show that the ovaries and/or adrenals were secreting androgens in these hirsute patients. Saline infusion brought about minor changes in peripheral and left ovarian vein steroid levels; however, episodic fluctuations occurred in the adrenal vein samples. Adrenocorticotrophic hormone infusion brought about dramatic increases in adrenal vein steroid concentrations, while ovarian vein concentrations were unaffected, compared with peripheral steroid levels. Human chorionic gonadotropin (HCG) infusion brought about increases in left ovarian vein steroids in some patients; however, those patients with corpus luteum on the right ovary or under chronic ovarian suppression did not respond to HCG. HCG was ineffective in altering adrenal steroid secretion. It was concluded that selective venous cannulation may be of some use when the ovary is the site of excessive androgen secretion. However, care must be taken in interpreting results when a corpus luteum is present in the contralateral ovary. Interpretation is difficult when the adrenal is suspect, because of the pulsatile nature of adrenal secretion or the possibility of stress-induced secretion.

Adolescent↗

"Timing" of ovulation by laparoscopy and evaluation of some physico-chemical parameters.

The Authors describe the laparoscopic aspects of spontaneous human ovulation and correlate it with the evaluation of basal body temperature, the total urinary oestrogens, pregnanediol and urinary LH and some hematic values of 17-beta-estradiol, 17-alpha-Hydroxyprogesterone and rogesterone. They find that the rise in temperature and the oestrogenuria peak precede ovulation by some hours in the great ovulation by sompe hours in the great majority of cases. They analyze the validity of the other parameters studied, and show a relatively constant behavior, with regard to ovulation, in the mean evaluation of several cases. In the individual analysis, on the contrary, this relation is difficult to find and less significant. The Authors stress the importance of comparing the physico-chemical evaluations with the biological phenomenon of ovulation directly ascertained by means of laparoscopy.

Body Temperature↗

[Plasma concentrations and urinary excretion of gonadotropins in azoo and oligospermia. Relationship with spermatogenesis and plasma concentration of androgens (author's transl)].

Plasma concentrations and urinary excretions rate of gonadotropins, testosterone, delta 4-androstenedione, dehydroepiandrosterone and 17 and 17 alpha-hydroxyprogesterone plasma concentrations have been studied in 69 patients with oligo or azoospermia and compared with results obtained in 30 normal control subjects. A sperm count and a caryotype have been done in all patients and a testicular biopsy in 35. Analysis of the histo-hormonal correlations does not show a particular stage of spermatogenesis associated with a modification in FSH production. There is a quantitative relationship between spermatogenesis and FSH production. Plasma testosterone is low and LH production normal in excretory azoospermia. In the other patients plasma testosterone is also low but associated with an increased production of LH. Finally there is a direct relationship between urinary excretion of LH and FSH in both normal subjects and patients, suggesting a modulation by specific factors of a common regulation of the secretion of both gonadotropins.

Adult↗

Progesterone concentration in placenta, molar tissue, and ovarian theca lutein cyst.

Progesterone concentrations in 2 full-term normal placentas, molar tissue from 3 cases of hydatidiform mole were measured by competitive protein binding. Sephadex LH-20 column chromatographic separation of extracts from these tissues showed that, in placental and molar tissue, 85 to 95% of the extracts were progesterone and very small amounts of 20 alpha-dihydroprogesterone and 17 alpha-hydroxyprogesterone. The concentration of progesterone in the placenta were 368.8 and 317.2 ng/g tissue, respectively, while in molar tissue the concentration were 2474.5, 1974.6, and 4146.0 ng/g tissue, respectively. Progesterone concentration in ovarian tissue was between 1121;2 and 1440.9 ng/g tissue. It is suggested that the high concentration of progesterone in molar tissue reflects functional capacity of the abnormal trophoblast in progesterone synthesis and accumulation of progesterone due to absence of a fetus. The lower concentration of progesterone in the ovary in molar pregnancy would appear to suggest that the ovary is a secondary source of progesterone in molar pregnancy.

Chorionic Gonadotropin↗

[A case of virilizing adrenal cortical adenoma whose steroid profile evokes a partial 21-hydroxylase deficiency (author's transl)].

The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17 alpha-hydroxyprogesterone and its urinary metabolites have been identified and quantitated gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. A of the fifty-five identified steroids thirteen were compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxtlase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.

Adenoma↗

[Characteristics of the ovarianc cycle in the baboon (Papio hamadryas)].

The dynamics of estradiol, estrone, 17 alpha-hydroxyprogesterone, progesterone and 20 alpha-dihydroprogesterone were investigated in the blood plasma of the pavian (papio, hamadryas) with regard to the menstrual cycle and in comparison with the human. Furthermore results were presented about the basal temperature, the fern phenomenon and the development of the sex-skin in the pavian.

Algestone↗

Serum progesterone and estradiol in pregnant women selected for progestagen treatment.

Patients with two or more previous spontaneous second trimester abortions and vaginal cytology indicating a poor progestational response in current pregnancies were selected for treatment with Provera (medroxyprogesterone acetate) and/or Delalutin (17 alpha-hydroxyprogesterone caproate). Serum was examined serially for progesterone (P) and estradiol (E) by radioimmunoassay. Serum from 174 untreated patients with no known complications ranging from 6--40 weeks gestation provided normal distribution data. Of 14 progestagen-treated patients, four aborted during the second trimester. These all had chronically low (greater than 50% of observations were less than 1 standard deviation of the normal population) or falling P/E ratios. The rest delivered normal full-term infants although five of the 10 had chronically low P, seven had chronically low P/E ratios, and in one other P/E was falling. Chronically high E contributed to the low P/E ratio in three cases. Thus, these selected cases with poor obstetrical histories demonstrated steroid patterns outside the +/- 1 standard deviation range, although the steroid levels were still within the normal range. Serum progesterone and estradiol analysis may eventually be useful in identifying patients who will best respond to progestagen treatment.

Abortion, Habitual↗

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↗

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↗

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↗