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One case of intra-abdominal seminoma with persistent müllerian duct syndrome is reported. Literature is reviewed and guidelines for management of such are suggested.

With a view to augment the cytochemical localization characterization and, probable functional significance of mucosubstances in the ovotestis in the reproductive physiology of land pulmonates, the mucosubstances were investigated in the ovotestis of a land snail, Semperula maculata (Stylommatophora) in the seasonal breeding-aestivation cycle. Widely accepted, recent and well-established histochemical techniques were emoloyed. The results showed that the cells in the germinal epithelium of the follicular wall, were endowed with a capacity of synthesis of neutral muco-substances. They also contained glycogen. The nurse cells contained neutral mucosubstances and glycogen in them, while maturing ovum contained hyaluronic acid and protein. Among all the male germ cell stages, only matured sperms showed sialoglycoprotein in their heads and glycogen in the tails. The seasonal variations in the mucosubstances showed that the synthesis of the mucosubstances in the male germ cells of the ovotestis was initiated at the end of the breeding season and attained a maximum in the post-breeding season. Most strikingly the presence of the sperm in the follicular cavity was a permanent feature throughout the seasonal breeding-aestivation cycle of the snails. The synthesis of the mucosubstances in the ovum and the nurse cells was initiated somewhat earlier in the post-breeding season and attained a peak prior to the active breeding season. The importance of the mucosubstances synthesised by the different cells of the ovotestis, is discussed with reference to the reproductive physiology of the snails.

A male pseudohermaphrodite rat mutant showing a blind-ending vagina, small undescended testes, rudimentary male sex accessory organs and XY karyotype was investigated. Genetic analysis revealed an autosomal single recessive transmission of this defect and indicated that the gene action is restricted to males. Microscopic examination showed an absence of typical Leydig cells in testes of the mutant. Plasma concentrations of testosterone were extremely low and the values were comparable to those of castrated male rats and did not change after castration and/or after administration of hCG. Plasma concentrations of LH and FSH were remarkably high and the values were comparable to those of long-term castrated normal male rats which declined to basal levels after administration of exogenous testosterone. Weights of thymus and adrenal glands decreased and weights of preputial glands, kidneys and male accessory sex organs increased in response to exogenous testosterone. These results indicate that the primary defect in the mutant is an androgen deficiency probably due to a Leydig cell agenesis in the testes.

The conversion of [1,2-3H]testosterone to [3H]dihydrotestosterone has been assessed in fibroblast monolayers grown from skin biopsies of foreskin, scrotum, and various nongential skins from 31 control men who varied in age from newborn to 25 years and three 46,XY subjects with hereditary male pseudohermaphroditism. Under the standardized conditions utilized in this study, the rate of dihydrotestosterone formation was greater in fibroblasts grown from genital skin (foreskin and scrotum) passages exhibit the same differentiation in dihydrotestosterone formation as the skin from which the fibroblasts were grown. Furthermore, 5alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, exhibits apparent similar substrate specificity in control foreskin fibroblasts and in the foreskin itself. Fibroblasts grown from the foreskin of two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive disorder of phenotypic sexual differentiation, showed a marked deficiency in the capacity to form dihydrotestosterone. In contrast, fibroblasts grown from the scrotum of one 46,XY male with familial incomplete male pseudohermaphroditism, type 1, an apparent X-linked disorder of phenotypic sexual differentiation, formed dihydrotestosterone at a normal rate.

Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product.

The affinity and turnover of the specific dihydrotestosterone binding protein have been assessed in fibroblasts cultured from genital skin from a variety of control subjects and from 4 patients with incomplete hereditary male pseudohermaphroditism due to androgen resistance (incomplete testicular feminization and Reifenstein syndrome). Whereas the amount of dihydrotestosterone binding in the 4 mutant cell strains is low, both the affinity of the protein for dihydrotestosterone as assessed by the concentration at which half-maximal binding occurs (averaging 0.2 nM) and the turnover of the binding protein (average half-life of 11--13 h) are within the normal range. Since no qualitative abnormality could be detected, these data suggest that the mutations in these two disorders affect the synthesis of the dihydrotestosterone binding protein.

Polycystic ovaries were found in a 16-year-old female with congenital absence of vagina, male-like external genitalia, and congenital adrenal hyperplasia. Masculinization was sufficiently severe to cause the patient to be reared as a male. Biochemical studies of ovarian tissue revealed hyperactivity and an imbalance of enzyme systems concerned with steroid-hormone biosynthesis, which led to production of large amounts of androgens. The pathway towards estrogens was preserved but less efficient than normal. Urinary steroid metabolites before and after hysterectomy and bilateral salpingo-oophorectomy revealed an absence of Porter-Silber chromogens and tetrahydrocortisone. Excretion of aldosterone was normal and that of corticosterone slightly higher than normal. The patterns of urinary 17-ketosteroids, pregnanediol, pregnanetriol and pregnanetriolone were similar to those commonly seen in congenital adrenal hyperplasia with steroid 21-hydroxylase deficiency. Urinary estrogens after panhysterectomy were low, being in the post-menopausal range. The pathogenesis of polycystic ovaries and their possible contribution to masculinization are discussed.

This is the first report of a male with 17alpha-hydroxylase deficiency resulting in male pseudohermaphroditism, ambiguous external genitalia, absence of male secondary sexual characteristics, and gynecomastia at puberty. Diagnosis was based on extensive studies of steroid metabolism including the following: low urinary excretion of 17-ketosteroids and 17-hydroxycorticoids which did not increase after ACTH; no response of very low plasma testosterone and dehydroepiandrosterone to adrenocorticotropin (ACTH) or chorionic gonadotropin; and low urinary aldosterone and plasma renin which increased after dexamethasone. Secretion rates of 17-hydroxylated steroids, cortisol (F) and 11-desoxycortisol (S), were very low while desoxycorticosterone (DOC) and corticosterone (B) secretion rates were increased sevenfold. Results expressed as milligrams per meter squared per day were as follows: F, 1.3; S, 0.023; DOC, 0.35; and B, 16 (mean normal values were F, 7.5; S, 0.26; DOC, 0.055, and B, 2.2). Plasma gonadotropins were markedly increased (FSH, 106; LH, 364 mIU/ml). Testicular biopsies revealed interstitial-cell hyperplasia and early spermatogenesis. Karyotype was 46/XY. Pedigree showed no other affected member. At laparotomy ovaries, uterus, and fallopian tubes were absent, vas deferens was incomplete, and prostate was present. External genitalia consisted of small phallus, bifid scrotum, third-degree hypospadias, and small vagina. At puberty there was no growth of body hair or phallic enlargement. Biopsy of marked gynecomastia showed both ducts and acini. Testosterone administration produced virilization. Sexual ambiguity demonstrates strong dependence of external genitalia on androgens for male differentiation. Suppression of Müllerian structures occurred despite female levels of testosterone indicating this step in male differentiation is not testosterone dependent. Pubertal breast development in this male supports the concept of femaleness during ontogeny unless counteracted by male factors. Diagnosis of other adrenocortical enzymatic deficiencies is excluded by the steroidal studies. The clinical response to testosterone excludes testicular feminization. Deficiency of 17-hydroxylation must be added to the cause of male pseudohermaphroditism.

Although it has long been known that the lack of androgen dependent differentiation in patients with testicular feminization is secondary to end organ insensitivity, the molecular basis of this genetic disorder has not been elucidated. In the present report a rodent model for testicular feminization is described. The Stanley-Gumbreck pseudohermaphroditic rat has an inherited disorder characterized by a female phenotype, a male genotype and tissue insensitivity to androgens. Even though male differentiation does not occur when these animals are treated with physiologic doses of testosterone, some androgen dependent growth is evident when 100-fold larger doses of testosterone are given. Studies of androgen metabolism in the psuedohermaphroditic animals indicate that testosterone transport and metabolism to dihydrotestosterone are normal. However, intranuclear retention of dihydrotestosterone is defective. These findings suggest that the androgen insensitivity of the pseudohermaphroditic rat is due to an inherited abnormality of a regulatory protein which renders the nucleus of the cell incapable of concentrating androgens at their proposed intracellular site of action. The pseudohermaphroditic rats also have a defect of testicular and adrenal steroid synthesis in addition to the androgen insensitivity. The relation of these two abnormalities in rat and in man are discussed.

In 22 children with male pseudohermaphroditism, plasma concentrations of testosterone and dehydroandrosterone sulfate were measured before and after HCG stimulation. In ten of them, nitrogen retention was measured both before and during treatment with testosterone-propionate. The results of this investigation allow the patients to be classified in the following groups 1) nine in which both the testicular function and the end-organ sensitivity to androgens were normal; 2) nine patients had an abnormal testicular function; 3) four patients had the testicular feminization syndrome. In addition, in one adolescent patient with familial male pseudohermaphroditism and gynecomastia, the pattern of plasma androgens under basal conditions, after HCG and following gonadectomy, suggest that the patient had an incomplete 17-ketosteroid reductase defect.