Serum 17α-hydroxyprogesterone Research Articles

Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia.

Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are limited to differentiate subtypes. We explored metabolic characterizations and identified multiple diagnostic biomarkers specific to individual subtypes of CAH. Liquid chromatography-mass spectrometry-based profiling of 33 adrenal steroids was developed and applied to serum samples obtained from 67 CAH patients and 38 healthy volunteers. Within- and between-run precisions were 95.4% to 108.3% and 94.1% to 110.0%, respectively, while all accuracies were <12% and the correlation coefficients (r2) were > 0.910. Metabolic ratios corresponding to 21-hydroxylase characterized 21-hydroxylase deficiency (21-OHD; n = 63) from healthy controls (area under the curve = 1.0, P < 1 × 10-18 for all) and other patients with CAH in addition to significantly increased serum 17α-hydroxyprogesterone (P < 1 × 10-16) and 21-deoxycortisol (P < 1 × 10-15) levels. Higher levels of mineralocorticoids, such as corticosterone (B) and 18-hydroxyB, were observed in 17α-hydroxylase deficiency (17α-OHD; N = 3), while metabolic ratio of dehydroepiandrosterone sulfate to pregnenolone sulfate was remarkably decreased against all subjects. A patient with 11β-hydroxylase deficiency (11β-OHD) demonstrated significantly elevated 11-deoxycortisol and its metabolite tetrahydroxy-11-deoxyF, with reduced metabolic ratios of 11β-hydroxytestosterone/testosterone and 11β-hydroxyandrostenedione/androstenedione. The steroid profiles resulted in significantly decreased cortisol metabolism in both 21-OHD and 17α-OHD but not in 11β-OHD. The metabolic signatures with specific steroids and their corresponding metabolic ratios may reveal individual CAH subtypes. Further investigations with more substantial sample sizes should be explored to enhance the clinical validity.

SUN-360 Multi-Steroid Panels to Replace Dynamic Testing for the Diagnosis of Nonclassic 21-Hydroxylase Deficiency

Background: The diagnosis of nonclassic 21-hydroxylase deficiency (N21OHD) is considered in children with precocious pubarche, in the differential diagnosis of polycystic ovary syndrome, and in first-degree relatives of patients with 21OHD. Currently, the diagnosis of N21OHD requires cosyntropin (ACTH)-stimulated serum 17α-hydroxyprogesterone (17OHP4) measurements; in addition, 17OHP4 also derives from the ovaries, and basal 17OHP4 is often inconclusive. Objectives: To determine if a panel of steroid biomarkers can diagnose N21OHD in a single blood draw, circumventing the need for dynamic testing. Methods: Patients undergoing evaluation for N21OHD with ACTH stimulation at two tertiary referral centers were included in this study. The diagnosis of N21OHD was based on stimulated serum 17OHP4 concentrations of >1,000 ng/dl (30 nmol/L). Baseline serum samples were used for the quantitation of 22 steroids (18 unconjugated and 4 sulfated steroids) by liquid chromatography-tandem mass spectrometry. Mann Whitney U test was used for two-group steroids comparison. Logistic regression modeling with lasso penalty, combined with clinical knowledge (relevant due to high correlation between biomarkers) were implemented for the selection of a small set of steroids that best discriminate patients with N21OHD from controls. Results: A total of 72 patients (63 females, 9 males) who underwent ACTH stimulation testing, median age 28 (range 6-70 years) were included in this study. Of these, 24 patients (4 males) were diagnosed with N21OHD; the other 48 patients (5 males) in whom N21OHD was excluded served as controls. Age and sex distribution were similar between the two groups (p = 0.9 and 0.5, respectively). Steroids displaying the largest differences between the two groups included: 11-ketotestosterone, 11-ketoandrostenedione (11KA4), 21-deoxycortisol (21dF), 17OHP4 and 16α-hydroxyprogesterone (all higher in N21OHD), plus 11-deoxycorticosterone (DOC) and corticosterone (lower in N21OHD), p <0.0001 for all. Notably, testosterone, androstenedione and all four sulfated steroids were similar between N21OHD patients and controls, including when data analysis was restricted to females. Logistic regression modeling showed that a three-steroid panel incorporating 21dF, 11KA4 and DOC was highly accurate in diagnosing N21OHD in baseline serum samples (AUC, 0.98) and superior to basal 17OHP4. Other combinations of adrenal-derived steroids also provided better discrimination than basal 17OHP4 (AUC >0.97 vs. 0.93). Conclusion: A limited number of adrenal-specific steroids measured in a single baseline blood draw can diagnose N21OHD with high accuracy. Such steroid panels might circumvent the need of dynamic testing in most patients to diagnose or exclude N21OHD.

Reference intervals for serum 17α-hydroxyprogesterone and ultrasonographic adrenal gland sizes in healthy newborns

Background and objectives: Serum 17α- hydroxyprogesterone (17OHP) and bilateral adrenal sizes are pivotal for clinical practice in both diagnosis and treatment of congenital adrenal disorders during the first month of life. Our aims were to determine the reference ranges for serum 17OHP and bilateral adrenal gland sizes according to sex and age groups in healthy term newborns.Materials and methods: A total of 156 healthy newborns, aged 4–7 days (Group 1) or 26–30 days old (Group 2) were included in the study. Serum 17OHP concentration was measured in the morning by radioimmunoassay. The right and left adrenal glands’ width, length, and depth were measured with ultrasonography by the same radiologist and the volumes were calculated.Results: The clinical characteristics and serum 17OHP concentrations were similar in male and female newborns. Percentiles for serum 17OHP concentration and the volume of adrenal glands according to age groups and sexes were obtained. Mean 17OHP concentration was 4.67 ± 2.6 ng/ml and 4.49 ± 2.7 ng/ml at the first and fourth week of life, respectively (p > .05). There was a significant decrease in adrenal sizes during the fourth week of life. There was no significant correlation between serum 17OHP concentration and adrenal gland sizes.Conclusions: We have determined reference intervals for serum 17OHP concentration and bilateral adrenal gland sizes for healthy newborns. Although serum concentrations of 17OHP did not change significantly through the first month of life, our reference intervals for serum 17OHP concentration and adrenal sizes may improve clinical approach toward newborns who are suspected of adrenal disorder. We conclude that our reference intervals can guide for congenital adrenal screening regarding serum 17OHP concentration besides diagnosis of adrenal hypoplasia or hyperplasia with ultrasonographic adrenal gland sizes.

先天性副腎皮質過形成(21-hydroxylase 欠損型)のマス・スクリーニングに関する研究 : 濾紙血清 17α-hydroxyprogesterone 測定値の安定性および新生児期血清 17α-hydroxyprogesterone 濃度に関する検討

先天性副腎皮質過形成(21-hydroxylase 欠損型)のマス・スクリーニングに関する研究 : 濾紙血清 17α-hydroxyprogesterone 測定値の安定性および新生児期血清 17α-hydroxyprogesterone 濃度に関する検討

Serum AMH levels in the differential diagnosis of hyperandrogenemic conditions

ObjectiveTo investigate the diagnostic potential of anti-Müllerian hormone (AMH) in the differential diagnosis of various hyperandrogenemic conditions. Study designAmong 2241 consecutive women of reproductive age who were seen at a tertiary care university hospital with complaints of acne, hirsutism, androgenetic alopecia, and menstrual dysfunction (oligomenorrhea and/or amenorrhea), 107 patients with serum 17α-hydroxyprogesterone (17α-OHP) levels higher than 2ng/ml were recruited for this study. An ACTH stimulation test was performed, and basal serum hormonal parameters and AMH levels were measured for all patients. Results25 patients were diagnosed with late-onset congenital adrenal hyperplasia (LOCAH), and 59 patients with polycystic ovary syndrome (PCOS) had significantly higher serum AMH levels than all other groups. ConclusionAmong hyperandrogenemic patients with serum 17α-OHP levels >2ng/ml, serum AMH levels might be introduced as a marker to be utilized clinically in the differential diagnosis of hyperandrogenemic patients, especially for identifying patients with PCOS.

Relationships of Basal Level of Serum 17-Hydroxyprogesterone with that of Serum Androstenedione and Their Stimulated Responses to a Low Dose of ACTH in Young Adult Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

A single measurement of serum 17α-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R2 = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.

Endocrine correlates of pregnancy in the ring-tailed lemur ( Lemur catta): Implications for the masculinization of daughters

Female ring-tailed lemurs ( Lemur catta) are Malagasy primates that are size monomorphic with males, socially dominate males, and exhibit a long, pendulous clitoris, channeled by the urethra. These masculine traits evoke certain attributes of female spotted hyenas ( Crocuta crocuta) and draw attention to the potential role of androgens in lemur sexual differentiation. Here, hormonal correlates of prenatal development were assessed to explore the possibility that maternal androgens may shape the masculine morphological and behavioral features of developing female lemurs. Maternal serum 17α-hydroxyprogesterone, dehydroepiandrosterone sulphate (DHEA-S), ∆ 4 androstenedione (androst-4-ene-3,17,dione), testosterone, and 17β-estradiol were charted throughout the 19 pregnancies of 11 ring-tailed lemurs. As in spotted hyenas, lemur pregnancies were associated with an immediate increase in androgen concentrations (implicating early maternal derivation), followed by continued increases across stages of gestation. Pregnancies that produced singleton males, twin males, or mixed-sex twins were marked by greater androgen and estrogen concentrations than were pregnancies that produced singleton or twin females, especially in the third trimester, implicating the fetal testes in late-term steroid profiles. Concentrations of DHEA-S were mostly below detectable limits, suggesting a minor role for the adrenals in androgen biosynthesis. Androgen concentrations of pregnant lemurs bearing female fetuses, although less than those of pregnant hyenas, exceeded preconception and postpartum values and peaked in the third trimester. Although a maternal (and, on occasion, fraternal) source of androgen may exist for fetal lemurs, further research is required to confirm that these steroids would reach the developing female and contribute to her masculinization.

Serum 17α-hydroxyprogesterone concentrations during the reproductive cycle in healthy dogs and dogs with hyperadrenocorticism

To determine concentrations of 17alpha-hydroxyprogesterone (17OHP) in serum of healthy bitches during various stages of the reproductive cycle and in bitches with hyperadrenocorticism and to compare the dynamics of 17OHP with those of progesterone. Prospective evaluation study. 15 healthy sexually intact bitches and 28 spayed bitches with hyperadrenocorticism. 11 healthy bitches were evaluated during estrus, nonpregnant diestrus, and anestrus (group 1); 4 other healthy bitches were evaluated during pregnancy and after ovariohysterectomy (group 2). Cycle stages were determined via physical examination, vaginal cytologic evaluation, and serum progesterone concentration. Bitches with hyperadrenocorticism were evaluated once at the time of diagnosis (group 3). Serum hormone concentrations were determined with immunoassays. In group 1, the serum 17OHP concentration was significantly higher in diestrus (median, 1.8 ng/mL) than in estrus (median, 1.1 ng/mL) and anestrus (median, 0.2 ng/mL) and higher in estrus than in anestrus. Changes in serum progesterone concentrations accounted for 22% (estrus) or 23% (diestrus) of the variation in serum 17OHP concentrations. In group 2, 17OHP and progesterone concentrations were significantly higher during pregnancy than after ovariohysterectomy. The serum 17OHP concentration in group 3 was significantly lower (median, 0.2 ng/mL) than in group 1 in estrus and diestrus and in group 2 during pregnancy (median, 0.7 ng/mL) but was not different from 17OHP concentrations in anestrus or after ovariohysterectomy (median, 0.2 ng/mL). Serum 17OHP concentrations in healthy bitches increased during estrus, diestrus, and pregnancy and at those times were higher than in spayed bitches with hyperadrenocorticism.

Measurement of Serum 17.ALPHA.-hydroxyprogesterone in Newborn Infants by Stable Isotope Dilution-Gas Chromatography/Mass Spectrometry

Immunochemical measurement of serum 17α-hydroxyprogesterone (17OHP), the most important parameter for diagnosis of classical 21-hydroxylase deficiency (21OHD) in newborn infants, is known to be inaccurate due to the cross-reactivity of antibodies with a large quantity of fetal adrenal steroids. The aims of this study were 1) to establish reference values for the serum 17OHP level in Japanese newborn infants using non-immunochemical stable isotope dilution —gas chromatography/mass spectrometry (SID-GC/MS) and 2) to compare the serum 17OHP levels determined by SID-GC/MS with those determined by radioimmunoassay (RIA). The first study subjects were used for determination of reference values and included 57 healthy full-term newborn infants (4–5 d of age). The second study subjects were used for comparison of SID-GC/MS with RIA and included 27 healthy full-term newborn infants (3–6 d of age) and two subjects with neonatal transient hyper 17OHPnemia; these two subjects were 16 and 27 d of age, respectively. In the first study subjects, the intra-assay coefficient of variation for SID-GC/MS was 3% (n=5), the recovery rate was 98%, the sensitivity was 0.2 ng/ml, and the range of linearity was 0.5–200 ng/ml. The reference values for the serum 17OHP level determined by SID-GC/MS ranged from 0.3–1.5 (0.6) (ng/ml) (median). In the second study subjects, the serum 17OHP levels determined by SID-GC/MS were lower in one of the 27 subjects and both of the two subjects with neonatal transient hyper 17OHPnemia compared with the levels determined by RIA. Measurement of the serum 17OHP level using SID-GC/MS may be clinically useful for definitive diagnosis of classical 21OHD in newborn infants.

Partial 17alpha-hydroxylase/17,20-lyase deficiency–clinical report of five Chinese 46,XX cases

Objectives. To summarize the clinical characteristics of partial 17α-hydroxylase/17,20-lyase deficiency (17OHD) in 46,XX Chinese patients.Methods. Five cases of 46,XX partial 17OHD from Peking Union Medical College Hospital were studied retrospectively by summarizing and analyzing their clinical data. The molecular pathogenic mechanisms involved are discussed after reviewing the literature.Results. Both complete and partial 17OHD patients have hypergonadotropic hypogonadism and elevated serum levels of adrenocorticotropic hormone and mineralocorticoids. The clinical characteristics of partial 17OHD are different from those of complete 17OHD; patients with the former having various degrees of estrogenic and androgenic impacts such as the development of breasts and pubic hair, and oligomenorrhea or secondary amenorrhea. Elevated serum progesterone with or without elevated serum 17α-hydroxyprogesterone and recurrent ovarian cysts are typical manifestations of partial 17OHD. Furthermore, hypokalemic hypertension may be absent in partial 17OHD. The 46,XX partial 17OHD should be differentiated from pure gonadal dysgenesis, premature ovarian failure and polycystic ovarian syndrome. It has been reported that specific mutations of the CYP17 gene can cause partial loss of 17α-hydroxylase/17,20-lyase activities or dissociation between the 17α-hydroxylase and the 17,20-lyase functions. Oral contraceptive pills are effective for artificial menstruation, but not for the correction of hormone deficiency. A low dose of cortisol should be prescribed in the presence of hypokalemic hypertension.Conclusion. The congenital partial 17OHD should be included in the differential diagnosis of menstrual disorders. In these cases, elevated progesterone offers a valuable clue for further investigation.

Iprodione delays male rat pubertal development, reduces serum testosterone levels, and decreases ex vivo testicular testosterone production

Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to procymidone and vinclozolin. All three of these fungicides induce Leydig cell tumors in the rat testis in long-term studies and an endocrine mode of action has been hypothesized to mediate this effect. Although both procymidone and vinclozolin antagonize the androgen receptor (AR) in vitro and in vivo, IPRO does not appear to be an AR antagonist. We proposed that pubertal exposure to IPRO would delay male rat pubertal development and reduce testosterone production within the testis. Sprague–Dawley weanling rats were dosed by gavage with 0, 50, 100, or 200 mg/kg /day of IPRO from post-natal day (PND) 23 to 51/52. The onset of puberty (progression of preputial separation (PPS)) was measured starting on PND 37. Organ weights, serum hormones, and ex vivo testis steroid hormone production under stimulated (+human chorionic gonadotropin (hCG)) and unstimulated (−hCG) conditions were measured at necropsy. IPRO delayed PPS at 100 and 200 mg/kg/day and decreased androgen sensitive seminal vesicle and epididymides weights at 200 mg/kg/day. Furthermore, IPRO increased adrenal and liver weights at 200 mg/kg/day, presumably by different mechanism(s) of action. Serum testosterone levels were decreased along with serum 17α-hydroxyprogesterone and androstenedione whereas serum LH was unaffected. IPRO reduced ex vivo testis production of testosterone and progesterone. Taken together, these results suggest that IPRO affects steroidogenesis within the testis, not through disruption of LH signaling, but possibly through enzyme inhibition of the steroidogenic pathway before CYP17. These data, along with the reported failure of IPRO to elicit an AR antagonism in vitro, provide evidence that IPRO differs from the dicarboximides procymidone and vinclozolin in that the effects on male rat pubertal development result from an inhibition of steroidogenesis and not AR antagonism.

Effects of melatonin administration on the clinical course of adrenocortical disease in domestic ferrets

To evaluate the effect of oral administration of melatonin on clinical signs, tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical disease. Noncontrolled clinical trial. 10 adult ferrets with clinical signs of adrenocortical disease (confirmed via serum steroid hormone concentration assessments). Melatonin (0.5 mg) was administered orally to ferrets once daily for 1 year. At 4-month intervals, a complete physical examination; abdominal ultrasonographic examination (including adrenal gland measurement); CBC; serum biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-hydroxyprogesterone concentrations were performed. Serum prolactin and dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and last examinations, and serum cortisol concentration was evaluated at the first and last examinations. Daily oral administration of melatonin greatly affected clinical signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean width of the abnormally large adrenal glands was significantly increased after the 12-month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-month evaluation. Compared with pretreatment values, serum 17alpha-hydroxyprogesterone and prolactin concentrations were significantly increased and decreased after 12 months, respectively. Results suggest that melatonin is a useful, easily administered, palliative treatment to decrease clinical signs associated with adrenocortical disease in ferrets, and positive effects of daily treatment were evident for at least an 8-month period. Oral administration of melatonin did not decrease adrenal gland tumor growth in treated ferrets.

Decreases in Ovarian Cytochrome P450c17 alpha Activity and Serum Free Testosterone After Reduction of Insulin Secretion in Polycystic Ovary Syndrome

Background Insulin resistance and increased ovarian cytochrome P450c17α activity are both features of the polycystic ovary syndrome. P450c17α, which is involved in androgen biosynthesis, has both 17α-hydroxylase and 17,20-lyase activities. Increased activity of this enzyme results in exaggerated conversion of progesterone to 17α-hydroxyprogesterone in response to stimulation by gonadotropin. We hypothesized that hyperinsulinemia stimulates ovarian P450c17α activity. Methods We measured serum steroid concentrations during fasting and the response of serum 17α-hydroxyprogesterone to leuprolide, a gonadotropin-releasing hormone agonist, and performed oral glucose-tolerance tests before and after oral administration of either metformin (500 mg three times daily) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome. Results In the 11 women given metformin, the mean (±SE) area under the serum insulin curve after oral glucose administration decreased from 9303±1603 to 4982±911 ...

Adrenal Tumor Complicating Untreated 21 -Hydroxylase Deficiency in a 5½-Year-Old Boy

• Objective. —A 5½-year-old boy presenting with virilization was diagnosed as having classic 21-hydroxylase deficiency complicated by an adrenal tumor. We attempted to document a reduction in the size of the tumor with glucocorticoid therapy. Design. —Case study. Setting. —Referral center. Intervention. —Glucocorticoid therapy was instituted for congenital adrenal hyperplasia. Surgery for the adrenal mass was deferred, and the size of the mass was monitored by serial ultrasonography. Results. —Baseline values of serum 17α-hydroxyprogesterone (186.6 nmol/L) and testosterone (24.7 nmol/L [7.1 ng/mL]) were elevated. After instituting steroid treatment, 17α-hydroxyprogesterone was suppressed (13.0 nmol/L), and testosterone remained undetectable on follow-up. However, the size of the mass increased during 6 months. Unilateral adrenalectomy performed at that time revealed a well-encapsulated adenoma in a hyperplastic gland. Conclusions. —Untreated classic congenital adrenal hyperplasia may be complicated by an adrenal tumor even at a young age. Suppression of adrenal androgens by glucocorticoid therapy was not accompanied by regression of the tumor in our patient. (AJDC. 1993;147:1321-1323)

Screening for Non-classic Steroid 21-Hydroxylase Deficiency in Japanese Women with Infertility and/or Hyperandrogenism

To identify patients with nonclassic steroid 21-hydroxylase deficiency, 137 Japanese women who visited our clinics because of infertility and/or hyperandrogenism were tested with adrenocorticotropin (ACTH) stimulation. In women with serum 17α-hydroxyprogesterone (17 OHP) values 60 min after ACTH administration higher than 5 ng/mL, ratios of 17-hydroxypregnanolone (5α) (17OH-PO) (5α) to the sum of tetrahydrocortisone (THE) and tetrahydrocortisol (THF) in 24-hour urine after ACTH-Z administration were determined. None of the women investigated showed any evidence of having the nonclassic form of this deficiency.

Serum 17α-hydroxyprogesterone in infants and children as measured by a direct radioimmunoassay kit

A direct 17 alpha-hydroxyprogesterone (17-OHP) radioimmunoassay kit was used for the assay of samples from 219 infants and children. The kit was used according to the manufacturer's protocol on unextracted serum or plasma and also on reconstituted material extracted from the serum with propanol-heptane. The extraction protocol recovers approximately 88% of 17-OHP. Patients were grouped as infants 3-90 days (96 subjects) or older children, adolescents and young adults 91 days-20 years (123 subjects). 17-OHP results by the direct and extraction protocols correlated but the slopes of the regression lines (0.43 and 0.63) differed in the two groups, indicating that only about 49% of the immunoreactive material measured by the kit in the infants was 17-OHP whereas the corresponding percentage was 72% in the older children. Despite this nonspecificity, the present antibody is much more specific for 17-OHP in the presence of neonatal plasma steroids than that used previously. Reference values were obtained for the two groups using the method with and without an extraction step. 17-OHP values on four untreated patients with CAH were clearly elevated at the time of diagnosis. It is recommended that when the kit is used with neonatal and infant samples, an extraction step should be incorporated to enhance specificity.

Adrenal steroids in post-menopausal women: Relation to obesity and to bone mineral content

Basal levels and ACTH-induced increments of serum 17α-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 post-menopausal women. The ACTH-induced increment of 170HP (Δ170HP) was negatively correlated to basal DHA and ΔDHA. Positive correlations were found between obesity, expressed as Broca's index, and ΔDHA and the ΔDHA/Δ170HP ratio. Bone mineral density was positively correlated to basal DHAS, ΔDHA, ΔDHAS and the ΔDHA/Δ170HP ratio, and negatively correlated to Δ170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to Δ 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Basal and adrenocorticotropic hormone-stimulated serum 17α-hydroxyprogesterone in men with idiopathic infertility

Basal serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations and the 17-OHP response to acute adrenocorticotropic hormone administration were studied in infertile men with idiopathic oligospermia to determine the prevalence of attenuated 21-hydroxylase deficiency. Mean (+/- standard error of the mean) basal serum 17-OHP levels in 50 infertile men (1.17 +/- 0.06 ng/ml) and 25 normal volunteers (1.09 +/- 0.08 ng/ml) were indistinguishable (not significant). However, two infertile men had 17-OHP levels which were above the normal range. Following the intravenous administration of 0.25 mg of synthetic adrenocorticotropic hormone (cosyntropin) to these two men and to eight additional infertile men, the mean increase in 17-OHP concentrations was 0.84 +/- 0.15 ng/ml, a response which was similar to that of normal men (0.94 +/- 0.26 ng/ml). No patient demonstrated the minimum fourfold rise in 17-OHP previously reported in men with attenuated 21-hydroxylase deficiency, suggesting the absence of this disorder among these subjects. This study suggests that subtle 21-hydroxylase deficiency is rare among infertile men with idiopathic infertility.

Hormone levels in serum and seminal plasma of men with different types of azoospermia.

Hormone concentrations in the serum and seminal plasma of 15 normozoospermic, 17 excretory azoospermic and 14 secretory azoospermic men were measured. The results indicate that: (a) serum FSH and LH levels are markedly elevated in secretory azoospermia, as compared with excretory azoospermia and normozoospermia; (b) serum 17 alpha-hydroxyprogesterone levels are somewhat raised in secretory azoospermia as compared with excretory azoospermia and normozoospermia; (c) serum testosterone levels are lower in both types of azoospermia with respect to normozoospermia; (d) in secretory azoospermia the oestradiol serum levels are relatively high and dihydrotestosterone serum levels relatively low, whereas the serum levels of these hormones in excretory azoospermia are similar to those in normozoospermic men; (e) in the seminal plasma of azoospermic patients the levels of prolactin, progesterone, testosterone, dihydrotestosterone and oestradiol were depressed, but only dihydrotestosterone levels could be of value in differentiating types of azoospermia because they are lower in secretory azoospermia. We suggest that the measurement of FSH, LH, 17 alpha-hydroxyprogesterone, dihydrotestosterone and oestradiol in serum and dihydrotestosterone in seminal plasma may be used in the differential diagnosis between secretory and excretory azoospermia when invasive tests are unavailable.

Regulation of Primate Testicular Luteinizing Hormone Receptors and Steroidogenesis

The testicular luteinizing hormone (LH) receptors of the rhesus monkey and human have many features in common, including high equilibrium association constant, marked species specificity, and relatively low binding capacity. We have, therefore, used rhesus monkeys as models for human LH-receptor regulation in vivo during gonadotropin treatment. In four adult male monkeys, treated with 10,000 IU human chorionic gonadotropin (hCG), serum and testicular steroidogenic responses were monitored at 24-h intervals during the following 4 d, and LH-receptor concentrations were measured by (125)I-hCG binding to 15,000-g particles prepared from testis biopsy specimens. In treated animals, serum hCG was maximal on day 1 at 322+/-16 ng/ml and declined to 24.4+/-2.3 ng/ml by day 4. Serum testosterone was increased threefold during the subsequent 4 d (from 6.5+/-2.0 to 18.6+/-4.4 ng/ml) but serum progesterone remained unchanged. In contrast, serum 17alpha-hydroxyprogesterone increased 12-fold to 5.5+/-0.5 ng/ml at day 1 and was increased fourfold during the subsequent 3 d. The LH-receptor binding capacity of the primate testis was reduced by 18.3+/-6.0% on day 1, 51.7+/-7.4% on day 2, and 45.3+/-2.4% on day 4. Occupancy of the LH receptors by endogenously bound hCG was significant on day 1 but was negligible by day 4. These data demonstrate that gonadotropin-induced LH-receptor depletion occurs in the rhesus testis and indicate that primate gonadotropin receptors are susceptible to the regulatory processes recently described in the rat. In addition, the simultaneous and disproportionate accumulation of 17alpha-hydroxyprogesterone indicates that 17,20-desmolase was rate-limiting under these conditions in the primate testis Leydig cell.