Feminizing and non-feminizing Sertoli cell tumors.
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Adolescent↗
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Fetal feminization induced by androgen insensitivity in the testicular feminizing syndrome: effect on marriage and maternalism.
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Adolescent↗
Differences in the urinary excretion of steroid metabolites after dehydroepiandrosterone-sulfate administration, in feminized and non feminized cirrhotic patients.
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11-Hydroxycorticosteroids↗
Studies on a feminizing human adrenal tumour. II. Biosynthesis in vitro of steroid hormones from testosterone-4-14C and androst-4-ene-3,17-dione-4-14C by a feminizing adrenal tumour.
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Adenoma↗
[Effect of tamoxifen on the feminization of chick embryo testis].
The problem was approached whether the feminizing action of oestrogens or androgens on the chick embryo testes could be antagonized by anti-oestrogens or anti-androgens. 100 micrograms of either tamoxifen, cyproterone acetate or compound RU 23908 were injected into the chick embryo after 4 days of incubation and 100 micrograms of either oestradiol benzoate or diethylstilboestrol or 1 mg of either androsterone, dehydroepiandrosterone, 5 alpha-dihydrotestosterone or 5 alpha-androstanedione were given one day later. The surviving embryos were sacrificed when 14-17 days old and their gonads were examined morphologically and in some cases also histologically. Control embryos were only given oestrogens or androgens. Out of 20 surviving embryos treated with oestradiol only, 10 were genetic females and 10 strongly feminized males. After tamoxifen treatment, out of 20 embryos, 11 were females, 7 normal males and 2 slightly feminized males. Thus, tamoxifen suppressed the feminizing action of oestradiol. It antagonized also the feminizing action of diethylstilboestrol. Neither cyproterone acetate nor compound RU 23908 suppressed the feminizing action of androsterone or diethylstilboestrol. But tamoxifen interfered with the androgens, preventing the feminization of the testes. It is suggested that androgens bind to the oestrogen receptor.
Androgen Antagonists↗
The effects of different types of neonatal feminization and environmental stimulation on changes in sex-associated activity/spatial learning skills.
This research programme commenced in West Africa, where it was found that individuals with kwashiorkor gynaecomastia were feminized. This was also reinforced by the interacting dominant maternal socialization practices (Dawson, 1966). This was confirmed with feminized responses for adult male rats, on the Tolman-Maze (Dawson, 1972), while as well confirmed neonatally, for both feminized male and female rats (Dawson, Cheung and Lau, 1973, 1975). The present experiment tests the interacting effects of various levels of environmental stimulation, high, normal and low (Levitsky and Barnes, 1972), using feminized male rats. Thus castration, oestrogen and castration, and oestrogen feminized males, were contrasted with male and female controls. The results confirmed the physiological growth curves and other anatomical differences. As well, the activity data confirmed the hypothesis, for the combined samples (where high Ns mean more reliability) and also the environmental stimulation (F ratio: d.f. 18 and 57, 11.37, p less than 0.001; low Ns here mean lower reliability). However, for the symmetrical maze, the results for the combined samples, were not as convincing as in Dawson et al. (1973, 1975), although the environmental stimulation produced significant results in many cases, including a significant interaction for the analysis of variance (F ratio: d.f. 18 and 57, 3.12 p less than 0.001).
Adolescent↗
Relationship between masculinity and feminity in drinking in alcohol-related behavior in a general population sample.
The relationship between gender-related personality traits, on one hand and drinking, permissiveness towards drinking, and social as well as personal problems associated to drinking on the other, was studied in a general population sample from the City of Morelia, Mexico. Four gender-related traits scales were used for measuring assertive and aggressive masculinity and affective and submissive feminity, in addition to a standardized questionnaire for assessing drinking and other associated behavior. Some of the main results showed that people with high scores in affective feminity were less willing to allow drinking. Men who adopted a submissive feminine role and women with high masculine aggressive scores were more permissive as regards drinking. Among men, assertive masculine and affective feminine traits were more characteristic among those who drank than among abtainers. Drinking among women was related to liberal attitudes towards drinking and to aggressive masculinity. As regards the number of drinks consumed per month, assertive masculinity and liberal attitudes among men and affective feminity and liberal attitudes among women predicted the number of drinks. Affective feminity was negatively related to drinking. Regarding drinking-associated problems, frequency of drunkenness and submissive feminity among males predicted greater personal and social problems. Among women, drunkenness frequency and number of drinks were the most significant predictors. Contrary to what has been found in other countries, gender was a better drinking predictor than gender-related personality traits.
Adolescent↗
Studies on testosterone metabolism in subjects with testicular feminization syndrome.
The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17beta-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5alpha-androstane-3alpha,17beta-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5alpha-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5alpha-reduction of this substrate seems very unlikely. The metabolic abnormalities observed in patients with testicular feminization syndrome may be reproduced in normal males by estrogen treatment. Nevertheless, the sensitivity of the patients to estrogen seems to be 10 times greater than that of normal males. This sensitivity was appreciated from the reduction of radioactive testosterone intravenously injected to urinary 17beta-hydroxy-5alpha-androstan-3-one and androstanediol and also from the level of plasma binding for testosterone. This level was significantly higher (P < 0.05) in patients with feminizing testes than in normal males. The level increased dramatically after administration of a low dose of estrogen whereas this effect was not observed in normal males under the same experimental conditions. In light of these results the defect of extrahepatic 5alpha-reduction of testosterone observed in patients with feminizing testes does not necessarily reflect an enzymatic impairment but might be related to an abnormal synthesis of plasma binding protein(s) under the effect of circulating estrogens so that an abnormally small amount of unbound testosterone may be available in target cells for 5alpha-reduction.
Adult↗
Continuous infusion of growth hormone feminizes hepatic steroid metabolism in the rat.
The metabolism of 4-[4-14C]androstene-3,17-dione was studied in the microsomal fraction of rat livers after continuous administration of human GH (hGH) in Alzet osmotic minipumps under varying conditions. hGH caused a complete feminization of hepatic steroid metabolism (i.e. increased the 5 alpha-reductase and decreased the 6 beta- and 16 alpha-hydroxylase activities) in normal male rats when infused at a rate of 5 microgram/h for 7 days. Hypophysectomy and castration or adrenalectomy and thyroidectomy of male rats did not reduce the feminizing capacity of hGH, indicating that the adrenals and the thyroid gland are not involved in the mediation of the feminizing effect of hGH. The same dose (5 microgram/h for 7 days) of hGH was also able to refeminize the liver steroid metabolism in hypophysectomized-ovariectomized female rats. The effect of the homologous hormones, rat PRL and rat GH on hepatic steroid metabolism was also investigated. Either hormone was infused at a rate of 10 microgram/h for 7 days, a dose which was sufficient to increase the serum level of the hormone in hypophysectomized animals. No feminizing effect was seen after the administration of rat PRL, whereas rat GH caused a partial feminization of hepatic steroid metabolism in hypophysectomized male animals. It is concluded that GH or a hormone related to GH is involved in sexual differentiation of liver steroid metabolism.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Origin of estrogen in normal men and in women with testicular feminization.
The purpose of this study was to quantify the various sources of estrone (E1) and 17 beta-estradiol (E2) production in normal men and in women with testicular feminization. The mean production rate of E1 in four young adult men was 58 micrograms/24 h, while that of E2 was 44 micrograms/24 h. In these men, E1 production could be accounted for totally by extraglandular formation through 1) aromatization of plasma androstenedione, 2) conversion of E2 which was formed from the aromatization of plasma testosterone, and 3) conversion of secreted E2. In these men, only 12 micrograms or less of E2 production could not be accounted for by extraglandular formation from plasma C19 precursors, and is presumed to have arisen by testicular secretion. In six women with testicular feminization, the mean production rate of E1 was 99 micrograms/24 h, while that of E2 was 77 micrograms/24 h. THe amount of E2 production that arose by glandular secretion could be computed in four of these women and was considerably greater than that found in the young adult men. In these women with testicular feminization, an average of 44 micrograms/24 h E2 could not be accounted for by extraglandular formation and is presumed to have arisen by testicular secretion. The mean plasma production rate of testosterone in the normal men was 5.7 mg/24 h, while that in the women with testicular feminization was 8.3 mg/24 h. However, the range of plasma production rates of testosterone in the women with testicular feminization was large (1.3--17.0 mg/24 h).
Adolescent↗
[Rudimentary uterus in testicular feminization (author's transl)].
The absence of uterus has been regarded by a number of authors as a condition for the diagnosis of testicular feminization, although cases with a rudimentary uterus have been reported. However, their number within the framework of this syndrome cannot be exactly determined. In the present report on a 22 year-old patient with testicular feminization and uterus bicornis solidus a double uterus malformation identical with that described in the Mayer-Rokitansky-küster syndrome was found. Forms of testicular feminization with rudimentary uterus in genetically-male individuals may be explained by the absence of androgens, or the absence of reactivity on the part of the target organ, and a simultaneous disturbance (lessening) of the function of the so-called X-factor (oviduct repressor) during early embryonal development. Our own observations, as well as reports in the literature, suggest a theory according to which testicular feminization may be regarded as a series of morphological variants, from male-oriented forms with vaginal aplasie, hypertrophy of the clitoris and male distribution of pubic hair, to female-orientated ones with a vagina of normal length and a rudimentary uterus. The absence of a uterus as a condition for the definition of the syndrome can be maintained only so far as no cases have, as yet been observed with a normally-developed uterus in a typical position. The karyogram showed a small Y-chromosome. Functional anomalies may only be surmised, since Y-anomalies are frequent (3% in a random collection). The morphology of the testes mirrored the functional embryonal insufficiency (pre-pubertal, undifferentiated testicular tissue with a varying amount of stroma and Leydig cells); the basal excretion of testosterone, 17-ketosteroid fractions and pregnane in the 24-hour urine was within the normal range for males. Oestrogen production over and above the "adrenal values" was also present. The values for plasma testosterone, which are in accordance with those of males of a similar age, are considered as indicating the importance of "androgen resistance in the periphery" as a factor in the aetiology of testicular feminization.
17-Ketosteroids↗
Hormone pattern in pharmacologically feminized male transsexuals in the California State prison system.
The hormonal profile of 40 transsexual inmates from a pool of 86 inmates in the California State prison system was studied before and after therapy with feminizing hormones. Clinical and social data were obtained on all 86 inmates; the incidence of human immunodeficiency virus (HIV) seropositivity was examined in 76 of the 86 individuals. Despite similar degrees of feminization in all 40 individuals in whom hormonal studies were performed, variable suppression of serum testosterone concentrations was present. Based on their testosterone concentrations while on feminizing hormone therapy, the transsexual inmates could be divided into three groups. In Group I (the "suppressed" group), the serum testosterone concentrations were markedly depressed (less than 10 ng/dL); in Group II (the "non-suppressed" group), the values of testosterone were normal (446 to 1072 ng/dL); and in Group III (the "intermediate" group), the testosterone values were between those of the suppressed group and the nonsuppressed group. We speculate that feminizing hormone therapy may induce the development of a state of target hormone resistance to testosterone that results in similar degrees of feminization independent of the circulating concentrations of testosterone. The incidence of HIV seropositivity (3/76) was considerably less than anticipated based on previous studies in populations at high risk for developing the acquired immunodeficiency syndrome.
Adult↗
Sex-specific proteins in normal chick embryo gonads and testis feminized by oestrogen treatment: a two-dimensional gel electrophoresis investigation.
Gonads dissected from 17-day-old normal chick embryos, as well as testes feminized by oestrogen treatment, were labelled in vitro with [35S]methionine and [14C]leucine. The patterns of cytosolic protein synthesis by the gonads were analysed using two-dimensional (2-D) polyacrylamide gel electrophoresis. In the feminized testis, two female-specific proteins appeared, the rate of synthesis of four testis-specific proteins was decreased, and quantitative variations of other synthesized proteins in relation to sex were detected. This altered protein synthesis indicates that the protein synthesis of the testis feminized by oestrogen treatment has in part become similar to that of a normal ovary. The synthesis of female-specific proteins in the feminized testis raises the question of their role in normal ovarian differentiation.
Animals↗
Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus.
The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally "feminized" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of "feminizing factor" from the female pituitary that is responsible for the "feminization" of the basically "masculine" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary "feminizing factor" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.
Androstane-3,17-diol↗
Induction of estrogen-independent persistent vaginal cornification in cyproterone acetate (CA)-induced feminized male mice.
Pregnant ICR/JCL mice were treated with 6 mg of cyproterone acetate (CA) from days 14 to 20 of pregnancy to feminize male offspring. Feminized males delivered on day 20 of pregnancy by cesarean section were castrated the same day, injected with estradiol-17beta(E2) or sesame oil from the day of delivery (=day 1) to day 10 and sacrificed on day 60. In oil-injected feminized males, the vaginal epithelium was atrophic and did not show cornification. In feminized males given 20 microgram E2 neonatally, the vaginal epithelium exhibited well-differentiated stratified squamous organization, but was not cornified in seven out of the nine mice of this group. In the mice treated with 50 microgram E2, persistent cornification was recognized most frequently in the posterior two-thirds of the vaginal epithelium which is considered to originate from the urogenital sinus. However, the incidence of cornification in the anterior one-third which may contain the epithelial cells of müllerian duct was low. These results provide supporting evidence for the possible participation of epithelial cells which come from the urogenital sinus in the development of estrogen-independent persistent vaginal cornification in neonatally estrogenized mice.
Animals↗
Testicular feminization syndrome in the neonate.
If we see a young, phenotypically female patient with an XY karyotype, it is of great importance to differentiate between the testicular feminization syndrome and gonadal dysgenesis. Patients with testicular feminization will always have normal testes, which are situated either in the ovarian fossa or in the inguinal canal. Patients with gonadal dysgenesis always have streak gonads. The risk of developing a malignancy in an abnormally located testis is very low, certainly before puberty, whereas the risk for dysgenetic gonads to develop a malignancy is high. Testes in patients with testicular feminization have an important endocrine function in puberty, whereas in gonadal dysgenesis patients they do not. For these reasons, in patients with testicular feminization, one should not remove the testes until the completion of puberty, whereas in patients with gonadal dysgenesis removal should be performed immediately upon recognition of the disorder.
Androgen-Insensitivity Syndrome↗
Purification of liver feminizing factor from rat pituitaries and demonstration of its identity with growth hormone.
The identity of the pituitary factor responsible for the maintenance of a female pattern of hepatic steroid metabolism and a female level of PRL receptors has been established. Fractionation of pituitary extracts revealed that only the GH fraction had the capacity to feminize liver metabolism of androstenedione (i.e. increase 5 alpha-reductase activity and decrease 16 alpha-hydroxylase activity) and to induce PRL receptors to a female level in hypophysectomized animals. The purification of pituitary GH was performed by chromatofocusing followed by gel filtration on Sephadex G-75. GH obtained from male or female pituitary glands showed an identical chromatographic behavior and both preparations had a mol wt of 22,000 and an isoelectric point of 6.1 when analyzed by analytical sodium dodecyl sulfate-gel electrophoresis and isoelectric focusing, respectively. The degree of homogeneity of GH varied between 93% and 97% as judged from sodium dodecyl sulfate-gel electrophoresis. Purified male and female GH were equally efficient in feminizing the liver metabolism. Since degradation of the native mol wt 22,000 form reduced the feminizing capacity, we believe that the intact hormone is needed for the feminization.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Haemophilia A in a patient with testicular feminization.
A case of typical haemophilia A in phenotypically "hairless" women aged 18 with complete testicular feminization (primary amenorrhea, absence of palpated gonads, negative sex chromatin, fluorescence of Y chromosome in interphase nuclei, caryotype 46, XY by common and fluorescent methods) is reported in this paper. Both diseases are of familial character with transmission through female line. The propositus' father did not suffer from haemophilia. Signs of Morris syndrome (delay of menses, absence of secondary hair) are present in the propositus' mother and sister. The propositus' niece, the daughter of her sister, also suffered from testicular feminization, but without any haemophilia, probably due to the crossing-over. The analysis of the pedigree gives no information in favour of sex-linked or autosome-dominant sex limited inheritance of testicular feminization. Haemophilia A in the propositus is characterized by the very low factor-VIII level-1.66%, and typical joints bleedings since 3 years. At the age of 18 the patient had major surgery for a haemophilic thigh pseudotumor. There was rapid consolidation of the fracture and contracture was erradicated. In spite of severe factor VIII deficiency the course of haemophilia in the propositus is clinically milder than in male haemophiliacs in her family and in the general population. The similar findings were reviewed in literature including the case of hemyzygous haemophilia with testicular feminization and described women-homozygotes. The suggestion is made that the course of haemophilia in the propositus is affected by the female phenotype. The psychologica status of the patient and the possibility of professional rehabilitation by surgical treatment is discussed. The need for detailed cytogenetical examination of the persons with "female" haemophilia or the other sex-linked diseases to establish the correct diagnosis and for exclusion of the possible mosaicism is discussed.
Amenorrhea↗