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The African region encompasses the highest undernutrition burden with the highest neonatal and infant mortality rates globally. Under these circumstances, breastfeeding is one of the most effective ways to ensure child health and development. However, evidence on human milk (HM) composition from African women is scarce. This is of special concern, as we have no reference data from HM composition in the context of food insecurity in Africa. Furthermore, data on the evolution of HM across lactational stages in this setting lack as well. In the MITICA study, we conducted a cohort study among 48 Central-African women and their 50 infants to analyze the emergence of gut dysbiosis in infants and describe the mother-infant transmission of microbiota between birth and 6 months of age. In this context, we assessed nutritional components in HM of 48 lactating women in Central Africa through five sampling times from week 1 after birth until week 25. Unexpectedly, HM-type III (Secretor + and Lewis genes -) was predominant in HM from Central African women, and some nutrients differed significantly among HM-types. While lactose concentration increased across lactation periods, fatty acid concentration did not vary significantly. The overall median level of 16 detected individual human milk oligosaccharides (HMOs; core structures as well as fucosylated and sialylated ones) decreased from 7.3 g/l at week 1 to 3.5 g/l at week 25. The median levels of total amino acids in HM dropped from 12.8 mg/ml at week 1 to 7.4 mg/ml at week 25. In contrast, specific free amino acids increased between months 1 and 3 of lactation, e.g., free glutamic acid, glutamine, aspartic acid, and serine. In conclusion, HM-type distribution and certain nutrients differed from Western mother HM.

Total cortisol as well as percentage and absolute free cortisol values were determined in 75 full-term, 88 premature and 38 small-for-age (born at term) infants in the first 3 months of life. Equilibrium dialysis and radioimmunoassay were used to estimate the percentage value of the unbound fraction and the value of total cortisol from which absolute free cortisol level was calculated, respectively. A systematic decrease in the free cortisol value was observed in all the three groups of infants during the study period (in full-term infants from 32.3 to 19%, in prematures from 36.6 to 20.8%, and in small-for-age infants from 32.3 to 19.2%). A comparison between the percentage values of free cortisol in the groups studied revealed only slight differences which were not significant. The absolute free cortisol values in full-term infants were highest immediately after birth (4.05 micrograms/dl), then they fell to the lowest level of 0.67 micrograms/dl observed between the third and fifth days of life, and increased afterwards reaching the level of 1.89 micrograms/dl in the third month. The absolute free cortisol values in premature newborns at 3-5 days of life exceeded the values observed in full-term subjects. The pattern of free cortisol in the prematures seems to be 'delayed' as compared with that in full-term newborns. The absolute free cortisol values in small-for-age infants were much more similar to those found in the full-term subjects, than to those in premature babies.

Indirect serotonergic agonists, whether promoters of 5-HT release such as fenfluramine (5 mg kg-1) or inhibitors of 5-HT uptake such as fluoxetine (10 mg kg-1), elicited in rats penile erections at a modest but significant level. Their effects were markedly potentiated by the beta-blocker tertatolol, (0.6-5 mg kg-1) which displays 5-HT1A receptor blocking activity, but not by the beta-blocker labetalol (6.25 and 25 mg kg-1), which lacks such activity. In addition, tertatolol, but not labetalol, potentiated penile erections induced by meta-chloro-phenylpiperazine (1 mg kg-1). Thus, it appears that increasing serotonergic transmission increases only moderately penile erections because of the functional opposition exerted by 5-HT1A (inhibition) and 5-HT1C (activation) serotonin receptors on this response.

Congenital adrenal hyperplasia (CAH) can be caused by a variety of defects in the functional gene encoding 21-hydroxylase (P450c21), which lies in the midst of the human leukocyte antigen (HLA) locus on chromosome 6. As a result, Mendelian genetics permit clinically distinct forms of CAH to be traced genetically by HLA and complement typing of family members. The recent cloning of probes for P450c21 now permits tracing of the affected gene directly. A consanguineous family had three members affected with three clinically distinct forms of CAH. Two of these individuals had identical extended haplotypes, including nine HLA and complement loci. Despite this extensive identity, the patterns of genomic DNA fragments digested with endonuclease EcoRI and detected by a P450c21 cDNA probe differed greatly in these two individuals. Thus, the DNA diagnosis of allelic variation was much more sensitive than the HLA diagnosis. Genomic DNA digested with endonuclease TaqI and probed with P450c21 cDNA revealed the 3.2-kilobase (kb) band, which is generally associated with the nonfunctional P450c21 A pseudogene, in all family members, and also revealed the 3.7-kb band associated with the functional P450c21 B gene in all family members except the severely affected index case. Probing of the same blots with a genomic probe also permitted examination of the adjacent downstream TaqI fragments, showing retention of both the 2.4-kb (A pseudogene) and 2.5-kb (B gene) fragments. Similarly, BglII-digested genomic DNA from all individuals contained both the 12-kb (A pseudogene) and 11-kb (B gene) bands. These data indicate that the basis of 21-hydroxylase deficiency in the index case was due to a homozygous gene conversion event and not to gene deletion. These results show that the DNA in and around the 21-hydroxylase gene is genetically very active, so that the usual generalization concerning linkage and inheritance may yield incorrect conclusions and diagnoses.

A randomized study of two protocols of human chorionic gonadotropin (hCG) treatment was performed in 183 prepubertal boys between 7 months and 12 years of age: protocol I, in which the boys were given 7 injections of 1,500 IU every other day, and protocol II consisting of 4 injections of 100 IU/kg at 4- to 5-day intervals. In both protocols, by the end of the test, testosterone had risen significantly to values within the normal adult male range. However, the amplitude of the rise was slightly but significantly lower using protocol II (4.08 ± 2.07 ng/ml) than protocol I (5.16 ± 2.73 ng/ml). It would thus appear that repetition of the hCG injection at intervals of less than 4 days is unnecessary, and that a total stimulation period of 2–3 weeks is sufficient. Although not correlated with testosterone levels, the success rates for treatment were similar in both protocols and comparable to rates reported in the literature.

The effect of indolamine derivatives on beta-endorphin (beta-end) release has been studied in vitro using rat anterior pituitary cells. Incubation of primary cultures for 2 h with 100 nmol/l of melatonin, serotonin or 5-methoxytryptamine significantly increased the beta-end release in response to 20 nmol/l of ovine corticotropin-releasing factor (oCRF). Incubation of the cultures with 100 nmol/l of L-tryptophan, 5-hydroxy-L-tryptophan, 5-hydroxytryptophol or 5-methoxytryptophol had no effect on basal or CRF-induced beta-end release. The effect of serotonin and melatonin was further tested in a superfusion system of dispersed rat anterior pituitary cells. Superfusion with oCRF (200 nmol/l) for 4 min elicited an immediate rapid increase in beta-end release which lasted 30-40 min. Simultaneous superfusion with melatonin (1 mumol/l) or serotonin (1 mumol/l) significantly increased the effect of oCRF pulses on beta-end release. We conclude that melatonin and serotonin are able to act directly on anterior pituitary cells to potentiate the effect of oCRF on beta-end release.

It is believed that the study of gonadal function of the child should be regarded as a whole, beginning with the fetus and ending with the adolescent. Gonadal function depends upon 3 levels of activities: 1) central level (extra-hypothalamic, hypothalamic, and anterior pituitary); 2) an intermediate level (gonadal and plasma), and 3) a peripheral level consisting of the target organs to which the hormonal message is directed. These activities determine both the expression of gonadal function (physical, physiological, or psychological) and the feedback regulation of gonadotropin secretion. There are 4 main phases of development of gonadal function: fetal, perinatal, prepubertal, and pubertal. The fetal phase begins with testosterone secretion around the 8th week in utero under the control of the chorionic gonadotropin. Gonadotropin secretion by the pituitary becomes established during the 12th week. During the 2nd half of fetal life, negative feedback becomes gradually established, appearing more rapidly in boys than in girls. In the perinatal phase, the hypothalamic-pituitary activity accounts for the testicular and probably ovarian secretion which has been demonstrated to occur during the 1st 6 months of life. Threshold sensitivity of the gonadostat to steroid inhibition appears high during the 1st 3 months of life, progressively declining to the very low level characteristic of childhood. The gonadostat is least active during the prepubertal phase, subsequently being more active under the influence of adrenocortical steroids. This hypothalamic activity accounts for the gradual increase of the pituitary and gonadal sensitivity to their respective stimuli. In the pubertal phase, the gonadostat threshold rapidly increases and secondary sexual characteristics and reproductive capacity start developing. 2 specific phenomena occur, large nocturnal discharges of luteinizing hormone and testosterone, and the establishment of positive feedback control by estrogens which permits ovulation.

Gonadotropins, prolactin (PRL), testosterone (T), Δ4-androstenedione, dehydroepiandrosterone sulfate and cortisol (F) levels were determined from 14 days before birth to term in 3 female an

Total and unbound testosterone and Delta(4)-androstenedione have been determined in 104 cord blood samples. The same sexual steroids and pituitary gonadotropins have been measured in 46 normal male infants aged 27-348 days and 34 normal female infants aged 19-332 days. In cord blood of female neonates mean total and unbound testosterone was 29.6+/-7.5 and 0.89+/-0.4 ng/100 ml, respectively (mean+/-1 SD); Delta(4)-androstenedione was 93+/-38 ng/100 ml. In male neonates mean plasma total and unbound testosterone was 38.9+/-10.8 and 1.12+/-0.4 ng/100 ml; Delta(4)-androstenedione was 85+/-27 ng/100 ml. In female infants testosterone concentrations remained constant during the 1st yr of life with a mean concentration of 7+/-3 ng/100 ml. Mean unbound testosterone and Delta(4)-androstenedione concentrations were 0.05+/-0.03 and 16.7+/-8.3 ng/100 ml, respectively. Mean plasma levels of follicle-stimulating hormone and luteinizing hormone were 8.7+/-3.3 and 12.9+/-7.7 mU/ml. In male infants mean plasma total testosterone concentration increased to 208+/-68 ng/100 ml from birth to 1-3 mo of age, decreasing thereafter to 95+/-53 ng/100 ml at 3-5 mo, 23.2+/-18 ng/100 ml at 5-7 mo, and reached prepubertal levels (6.6+/-4.6 ng/100 ml) at 7-12 mo. Mean unbound testosterone concentration plateaued from birth to 1-3 mo of age (1.3+/-0.2 ng/100 ml) decreasing to prepubertal values very rapidly. Mean Delta(4)-androstenedione concentration, although progressively decreasing during the 1st yr of life to 11.7+/-4.5 ng/100 ml, was higher than in the female at 1-3 mo of life (34+/-11 ng/100 ml). Mean plasma level of follicle-stimulating hormone was 6.7+/-2.9 mU/ml, and that of luteinizing hormone was 19.7+/-13.5 mU/ml, significantly higher than in the female. There was no correlation between gonadotropin and age or testosterone. The present data demonstrate that the testes are active during the first natal period. It is tempting to correlate this phenomenon to a progressive maturation of the hypothalamo-pituitary-gonadal axis. It is possible that the surge in testosterone occurring the first 3 mo could play a role in the future life pattern of the male human being.

Testicular response to human chorionic gonadotropin (hCG) was studied in male lambs. Adenosine 3':5'-cyclic monophosphate (cAMP), testosterone (T), delta 4-androstenedione and 17 alpha-hydroxyprogesterone content and cAMP and T production by dispersed interstitial cells were assessed in control and hCG-pretreated animals. Plasma T levels increased after hCG at 1, 4 and 8 weeks. Increments in the testicular content of cAMP, delta 4-androstenedione, and T were greater at 8 weeks and that of 17 alpha-hydroxyprogesterone and 125I-hCG binding to dispersed interstitial cells were identical at all ages. cAMP and T production by dispersed interstitial cells from nonstimulated animals and the response to hCG and choleratoxin were similar in all lambs. In contrast, cAMP and T production were higher at 1 week only in animals pretreated with hCG in vivo. These data are compatible with hCG-induced desensitization at 4 and 8 weeks.

A boy with adrenocortical carcinoma has been studied. The initial urinary 17-ketosteroid excretion was between 1700 and 2100 mg/day. Peripheral plasma levels of pregnenolone, 17-hydroxypregnenolone,dehydroepiandrosterone (DHA), androstenediol, testosterone (T) and the sulfate conjugates of these steroids were elevated. Plasma levels of androstenedione (Δ) were also high. The levels of these steroids in adrenal vein plasma were still higher except in the case of unconjugated T. The MCR and the blood production rates of T and Δ were elevated but were lower than their urinary production rates. The urinary production rates of DHAS and DHA were 2000 and 5100 mg/day, respectively. These results, considered in association with the specific activities of several urinary metabolites after injection of tracers (3H-T+14C-Δ, 3H-DHAS+14C-DHA and 3H-DHAS+14C-Δ) suggest that: 1. Urinary androsterone was diluted by precursors that did not pass through the plasma Δ pool. 2. Urinary T glucuronide was derived in pa...

Various corticosteroids (cortisol, tetrahydrocortisol or tetrahydrocortisone intravenously, 1 mg. per Kg. of body weight; 4-C14-cortisol intravenously, 1 microcurie; cortisol or cortisone acetate orally, 100 mg.) were administered to normal adult subjects. Blood samples were obtained at specific intervals following administration of steroid. 17-Hydroxycorticosteroid (17-OH-CS) extracts of red cells and plasma were prepared. In all cases, a significant fraction of the free 17-OH-CS of the various blood samples was associated with the red cells (average, 25.1 per cent; range, 17.7 to 36.5 per cent), whereas the total amount of the 17-OH-CS glucuronides was found in the plasma.

SUMMARY The concentration of oestrone (E1) and oestradiol (E2) in plasma was measured by a radioimmunological method. In five premenopausal women, ovariectomy provoked a significant fall in the concentrations of E1 and E2. In 11 subjects of both sexes with cancer, dexamethasone (20 μg/kg/day) caused a significant fall in the levels of cortisol (84 ± 9·5%) and E1 (55 ± 16%), but not in E2 (2 ± 18%). Ninety minutes after administration of tetracosactrin, the increase in concentration of cortisol (80 ± 30%) and of E1 (70 ± 49%) was highly significant: that of E2 (5 ± 12%) was not. Similar results were observed in four subjects during infusion of corticotrophin. In six subjects, plasma concentration of E1, androstenedione and dehydroepiandrosterone was higher in the adrenal vein than in a peripheral vein, but the concentration of E2 and of testosterone was similar in the two samples. In two men, the concentration of androgens and oestrogens was measured in plasma from a peripheral vein and in plasma of mixed origin from the renal and the spermatic vein. The level of E2 was higher in plasma from the renal—spermatic mixture than in that from the peripheral vein, but the concentration of E1 was similar. All these results suggest that: (1) the adrenal secretes only 17-oxo androgens and oestrogens whereas in the testicular secretion, 17β-hydroxylated compounds predominate; (2) in men, nearly all of the E2 is secreted directly or indirectly by the testes, but the main source of E1 is the adrenal; (3) in postmenopausal women, most of the E1 also derives from the adrenal gland.

Four normal adult males and a 7 year old boy with virilizing adrenocortical tumor received an intravenous injection of 7- 3 H-testosterone sulfate. Twenty-eight to 61% of the tritium injected was recovered in urine collected during the 14 days following the injection with 2.7–11.3% as TS and about 0.0015% as testosterone glucuronide. The disappearance curve of 3 H-TS from plasma was found to be represented by three exponentials during the 10–18 hours of study. The metabolic clearance rates ranged from 50 to 89 liters/M 2 /24 hours in the normal males and was 203 liters/M 2 /24 hours in the patient with virilizing adrenal tumor. Urinary productions and blood production of TS were similar ranging from 64 to 310 μ g/24 hours in normal males, and a value of 2,030 in the patient with virilizing adrenal tumor. Using various assumptions, it was speculated that about 1% of plasma T is converted to plasma TS, while about 0.15% of plasma TS is converted to plasma T.

Twenty-four patients with male pseudohermaphroditism have been studied. In all of them, plasma concentrations of testosterone (T) and dehydroepiandrosterone sulfate (DHAS) were measured before and after stimulation with HCG. Before puberty (21 patients), the mean plasma concentration at 40.5±10 ng/100 ml (sd) was similar to that found in normal children. After HCG administration, an abnormally low increase in plasma T was observed in 10 patients out of 24. Nitrogen retention was measured in 10 patients, both before and during treatment with testosterone propionate. A sharp rise in nitrogen retention was observed in all cases. In 9 patients, both testicular androgenic function and end-organ sensibility to androgens were normal.

Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.

Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features with desmosomes at cell-to-cell contacts and intermediate filaments in addition to secretory granules in the cytoplasm. Insulin and C-peptide were released in equimolar amounts in culture media. When challenged for 30 min with 16.7 mM glucose, 1 mM 3-isobutyl-1-methylxanthine, 4 mM tolbutamide, or 10−6 M glucagon, insulinoma cells responded by a 1.5-, 1.5-, 2-, or 3-fold increase, respectively, in insulin release above baseline levels. A 15-min challenge with 10−5 M isoproterenol increased insulin secretion by 1.85-fold. By indirect immunofiuorescence, an anti-insulin antibody reacted positively with cell cytoplasm, whereas anti-somatostatin and anti-glucagon antibodies did not. Insulinoma cell surface expressed class I MHC molecules but not class II molecules. Immediately after isolation, crude insulinoma cells were contaminated by 2% of DR+ cells from nonislet components that disappeared after several weeks in culture. The ability of insulinoma cells to stimulate allogenic T-lymphocyte proliferation was assessed by [3H]thymidine incorporation in mixed culture combinations. Crude insulinoma cells elicited a strong lymphoproliterative response with a stimulation index ranging between 3.5 and 7, whereas no stimulation was found after 1 mo in culture. It is postulated that absence of class II-positive cells in the stimulatory cell preparation conditioned this immune tolerance across the major histocompatibility barrier. These results obtained with human insulin-secreting cells underline the need of in vitro manipulation for the success of human islet allografts in insulin-dependent diabetes mellitus.

IPL (Institut Pasteur, Lyon) nude, hypoprolactinemic rats- exhibit delayed puberty and a complete lack of lactation. To characterize the secretion of circulating forms of prolactin (PRL) of these rats, PRL concentrations were measured in serum and pituitaries of males and females under various physiological conditions. Two assay methods, a radioimmunoassay (RIA) and a sensitive bioassay (NB2 BA) were employed. Normal rats of the Sprague-Dawley strain were tested simultaneously, as controls. The pituitary content of PRL, estimated either by RIA or by NB2 BA, in IPL nude males and females was similar to that of normal male and female rats. On the contrary, serum PRL levels of IPL male rats, measured by RIA or NB2 BA, were significantly reduced when compared to normal rats. in both groups, there was a close correlation between the results obtained by the two methods, the NB2 BA estimates being higher. However, the NB2 BA/RIA ratio was significantly decreased in serum from IPL nude rats compared to controls, indicating that the circulating form of PRL was less bioactive in this group. Castrated male rats injected with estradiol showed sharply increased PRL values as estimated by RIA or NB2 BA. The increase was greater (35-fold) in IPL nude rats then in normal rats (9-fold), but these increases resulted in serum PRL levels being similar in the two groups. However, the NB2 BA/RIA ratio remained significantly reduced in IPL nude rats. In female rats, PRL was measured during different physiological states: estrus, diestrus, pro estrus at 1000, 1200, and 1600 h and Days I and 21 of gestation and 2 days postpartum. PRL estimates by NB2BA or RIA in 1PL nude rats were decreased in all conditions, although the differences were not significant. However, the NB2 BA/RIA ratio was significantly decreased on the day of diestrus (1 ± 0.2 and 3.09 ± 0.52) for IPL nude and normal rats, respectively, during the day of estrus (2.06 ± 0.34 and 3.78 ± 0.54) and in the post -partum period (1.08 ± 0.14 and 2.17 ± 0.24) for IPL nude and normal rats, respectively. Serum rat placental lactogen II (rPL2) values were found to be similar in both groups of rats, perhaps accounting for normal mammary gland development during gestation in this new rat strain. We conclude that circulating PRL biopotency in IPL nude rats is sharply decreased. The relative bioactivity, as representated by NB2 BA/RJA ratio, was not corrected by estradiol injection, at least in the male rats. These findings could contribute to an understanding of the endocrine characteristics of this rat strain.

In order to evaluate thyrotropin function in the genetically hypoprolactinemic rat, (IPL nude), we measured by radioimmunoassay TRH hypothalamic content, pituitary TSH content and serum TSH, T3, T4, both in IPL nude and control rats at various times over the 24-hour period. Compared to normal rats, the hypothalamic TRH content in the IPL nude rat showed similar variations during the day, whereas a slight increase was observed during the night characterized by a significant difference at 20.00 h. Pituitary weight and TSH content were doubled in IPL nude rats; however, when expressed as micrograms TSH/micrograms protein or DNA, a significant increase was found only at 17.00 and 20.00 h. Serum TSH and total serum T3, T4 depicted similar variations although they were minute but nonetheless significant modifications, i.e. an increase of TSH at 17.00 and 23.00 h and a decrease of T4 at 11.00 h. However, only FT4 concentrations (and not-FT3) were slightly but significantly decreased in IPL rats over the experimental times. In conclusion, the slight increase in hypothalamic TRH and pituitary TSH contents and the absence of main associated variations of serum TSH, T3 and T4 do not lend support to the hypothesis that TRH could be the cause of the hypoprolactinemia of these rats. On the contrary, the observed thyrotropin axis variations might be rather interpreted as the consequence of it.

Because of its enzyme-inducing properties, which are thought to explain its lowering effect on neonatal hyperbilirubinemia, phenobarbital (PB) has been widely used as prophylactic treatment in neonatal jaundice. Experimental data suggesting that PB might have various effects on endocrine metabolism or regulation prompted us to investigate whether PB had some adverse effects on testicular or adrenal function in human neonates. A group (I) of 12 prematures given a single im injection of 10 mg/kg PB on the day of birth were studied longitudinally for 6 months and compared with untreated, premature (group II), and fullterm (group III) infants. Plasma testosterone (T), Δ4-androstenedione (Δ4), 17α-hydroxyprogesterone, and cortisol (F) were similar in the 3 groups at birth and before PB therapy. A postnatal rise in T and 17α-hydroxyprogesterone levels occurred in the 3 groups. Study of the temporal patterns showed that peak T levels were lower, and their decline beyond 2 months of age was more rapid, in group I...

Plasma concentrations of testosterone, D and DS, have been determined in 16 normal children before and after HCG stimulation. Mean testosterone levels were 31, 8 ± 10 mμg/100 ml. before HCG and 554 ± 121 mμg/100 ml. after HCG. D was studied in 6 children only. The mean values were 138 ± 40 mμg/100 ml. and 394 ± 204 mμg/100 ml. before and after HCG respectively. DS concentration was very low before the age of 7 years, increasing thereafter to reach levels very close to those found in adults before there was clinical evidence of the onset of puberty. In the group as a whole, the mean DS concentration before HCG was 27, 1 ± 16, 6 μg/100 ml. and after HCG 36, 4 ± 16, 9 μg/ 100 ml. the difference not being significant (p > 0, 05). However if subjects less than 8 years old were considered separately, the mean values were 5, 4 ± 2, 5 μg/100 ml. and 13, 9 ± 5, 5 μg/100 ml. before and after HCG and this difference is significant (p

The metabolic clearance rate (MCR) and blood production rate (BP) of testosterone (T) and dihydrotestosterone (DHT), the conversion of plasma testosterone to plasma dihydrotestosterone, and the renal clearance of androstenedione, testosterone, and dihydrotestosterone have been studied in man. In eight normal men, the MCR(T) (516+/-108 [SD] liters/m(2)/day) was significantly greater than the MCR(DHT) (391+/-71 [SD] liters/m(2)/day). In seven females, the MCR(T) (304+/-53 [SD] liters/m(2)/day) was also greater than the MCR(DHT) (209+/-45 [SD] liters/m(2)/day) and both values were less than their respective values in men (P < 0.001). In men the conversion of testosterone into dihydrotestosterone at 2.8+/-0.3% (SD) was greater than that found in females, 1.56+/-0.5% (SD) (P < 0.001). In five pregnant females the MCR(T) (192+/-36 [SD] liters/m(2)/day), the MCR(DHT) (89+/-30 [SD] liters/m(2)/day) and the conversion of testosterone into dihydrotestosterone (0.72+/-0.15%) (SD) were significantly less than the values found in nonpregnant women. In five females with hyperthyroidism, the MCR for testosterone and dihydrotestosterone were similar to those observed in pregnant females, but the conversion of testosterone into dihydrotestosterone (2.78+/-1.7%) (SD) was greater, and similar to that found in men. In men the production of dihydrotestosterone was 0.39+/-0.1 (SD) mg/day, 50% being derived from the transformation of plasma testosterone. In women the production of DHT was 0.05+/-0.028 (SD) mg/day, only 10% coming from testosterone. During pregnancy, the production of testosterone and dihydrotestosterone are similar to that in normal women. In three patients with testicular feminization syndrome (an adult with hyperthyroidism and two children) these two MCRs were greatly reduced compared to the normal females, but the conversion of testosterone into dihydrotestosterone was in the limits of normal male rangeIn the normal subjects the renal clearance of androstenedione was greater than that of testosterone and dihydrotestosterone. Less than 20% of the dihydrotestosterone and less than 10% of the androstenedione in the urine is derived from the plasma dihydrotestosterone and androstenedione.