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Transfection of Wolbachia in Lepidoptera: the feminizer of the adzuki bean borer Ostrinia scapulalis causes male killing in the Mediterranean flour moth Ephestia kuehniella.

Two species of Lepidoptera, Ostrinia scapulalis and Ephestia kuehniella, harbour Wolbachia, which are maternally transmitted intracellular bacteria that often cause reproductive abnormalities in arthropods. While the infection in O. scapulalis causes conversion of genetic males into functional females (feminization), that in E. kuehniella induces cytoplasmic incompatibility. In the present study, we investigated the relative importance of host and Wolbachia factors in the differential expression of reproductive alterations in these insects. We transferred the Wolbachia harboured by O. scapulalis to E. kuehniella in which the original infection had been cured by tetracycline treatment. The transfected strain of E. kuehniella expressed a maternally inherited, female-biased sex ratio. Unexpectedly, two lines of evidence suggested that the sex ratio distortion was due to male killing. First, higher mortality of young larvae was observed. Second, the removal of the transferred Wolbachia resulted in the recovery of a 1:1 sex ratio, whereas the removal of a feminizer should result in a male-biased sex ratio among offspring. To the authors' knowledge, this is the first report that a single Wolbachia strain can cause two distinct sexual abnormalities in different hosts. Our observations highlighted the importance of host-Wolbachia interactions in determining the phenotype of reproductive alterations.

Androgen-Insensitivity Syndrome↗

Studies of in vitro steroid metabolism by testis tissue from 'complete' and 'incomplete' forms of testicular feminization.

The in vitro steroid metabolism of testicular tissue from seven cases of testicular feminization was studied. Using radioactive steroid substrates of both C21 and C19 configurations, kinetic studies of these tissues showed that the major pathway of testosterone production was via the delta5 pathway, i.e. pregnenolone leads to 17 alpha-hydroxypregnenolone leads to dehydroepiandrosterone leads to androstenedione and androstenediol leads to testosterone, with the accumulation of dehydroepiandrosterone and androstenediol. This accumulation of dehydroepiandrosterone and androstenediol does not occur in similar incubations of normal human testis tissue. The seven cases of testicular feminization were classified as 'complete' or 'incomplete' forms of the syndrome by reference to clinical data and the histology of the testicular tissue. It was concluded that the biochemical differences between the two forms of the syndrome were the greater production and accumulation of C21 and C19 delta 4 steroids from the C21 and C19 delta 5 steroid precursors indicating the relatively greater activity of the C21-3beta-hydroxysteroid dehydrogenase-isomerase enzyme in the 'incomplete' form.

17-alpha-Hydroxypregnenolone↗

Laparoscopic gonadectomy for testicular feminization syndrome.

Laparoscopic gonadectomy was performed on a patient with complete androgen insensitivity (testicular feminization syndrome). In the case presented here, although the gonads were free, the omentum which was adhering to the right inguinal ring, possibly as a result of previous inguinal hernia repair, obscured the right gonad. The left gonad was located behind the sigmoid colon. We present our laparoscopic experience in managing this case of testicular feminization syndrome.

Adult↗

The testicular feminized rat: a naturally occurring model of androgen independent brain masculinization.

Although genotypically male (XY), the testicular feminized rat develops as an anatomic female because of an inherited deficiency in intracellular androgen receptors that prevents androgen imprinting of sexual primordia. However, the ability of testicular feminized rats to exhibit male-like sexual behavior and little feminine sexual behavior suggests that the brain can be masculinized without androgens.

Androgen-Insensitivity Syndrome↗

Feminizing adrenocortical carcinoma in a postmenopausal woman.

The successful surgical removal of a feminizing adrenal tumour in a postmenopausal woman is described. Most of these tumours are malignant and the pathological findings and the biological behaviour of the tumour frequently do not correlate, so that a careful follow-up is necessary. In the presence of vaginal bleeding in a postmenopausal woman endometrial carcinoma should be considered. If this has been ruled out and if oestrogens are elevated with low plasma gonadotrophins, a feminizing ovarian or adrenal tumour should be considered.

Adrenal Cortex Neoplasms↗

Testicular feminization syndrome: a report of three Ethiopian patients and a brief review.

The clinical features of 3 Ethiopian patients presenting with the complete syndrome of testicular feminization are described. All 3 were seen because of primary amenorrhoea. At laparotomy, one patient had testes located intra-abdominally, a second lodged in the inguinal canals and a third as masses in the labia majora. Also, one of these patients had bilateral inguinal herniae, a usual feature of this syndrome. Since the incidence of malignancy is high among individuals with undescended testes, they were removed in 2 patients. In the third patient, however, the testes were not removed because of delay in development of secondary sex characteristics. The literature on testicular feminization is also briefly reviewed.

Adult↗

Direct and mediated effects of testosterone: analysis of sex reversed mosaic mice heterozygous for testicular feminization.

Sex reversed mice are XX males carrying on one of their X chromosomes a translocation of the sex determining region of the Y (Cattanach's Sxr factor). The phenotype corresponds to the Klinefelter syndrome in man. The X linked Tfm (testicular feminization) mutation in the mouse is a frame shift in the androgen receptor gene leading to complete androgen insensitivity. Due to random X inactivation, sex reversed mice heterozygous for Tfm, are mosaics composed of a variable proportion of androgen insensitive X Tfm and androgen sensitive X+ wildtype cells. In the intersexual genital tract, Tfm cells are maintained as undifferentiated cells in the epididymal duct. To the distorted prostate lobes and bulbourethral glands they contribute some lobules of indifferent urethral glands. A large contribution of Tfm cells allows downgrowth of Wolffian and Müllerian ducts to form a vagina. In the external genitalia the stimulatory effect of testosterone is reduced leading to various degrees of feminization correlating with the proportion of Tfm cells present. In the mosaics effects of testosterone, mediated by local growth factors from the wildtype to the Tfm cells, can be distinguished from direct effects expressed only in the wildtype cells. Mediated effects are embryonic induction and morphogenesis of male organs and postnatal maintenance of organ structure and proliferation. The direct effect is cellular differentiation.

Androgen-Insensitivity Syndrome↗

Estradiol and para-chlorophenylalanine downregulate the expression of brain aromatase and estrogen receptor-alpha mRNA during the critical period of feminization in tilapia (Oreochromis mossambicus).

The period of maximal feminizing action of 17beta-estradiol (E(2)) upon sex ratio is before 10 days posthatching in tilapia (Oreochromis mossambicus). The effect of E(2) at this time is mimicked by para-chlorophenylalanine (p-CPA), a serotonin (5-hydroxytryptamine; 5-HT) synthesis inhibitor. The effect of E(2) on sexual differentiation may be mediated by the 5-HT system, which is consistent with the suggestion in mammals. The masculinizing actions of 17alpha-methyltestosterone (MT) are most potent later at up to day 20 of age, and may depend on MT induction of aromatase activity. In the present study, the effects of gonadal steroids and p-CPA on brain aromatase and estrogen receptor (ER) mRNA expression during the critical period of sexual differentiation were investigated. Treatment of tilapia with E(2) resulted in a significant decrease in the expression of brain aromatase and ERalpha between days 0 and 10, but not subsequently. The effect of E(2) at this time can be mimicked by p-CPA. Treatment of tilapia with MT, by contrast, resulted in a significant increase in brain aromatase, ERalpha and ERbeta mRNA expression when given between days 10 and 20. The downregulation of brain aromatase and ERalpha mRNA expression by E(2) before 10 days of age and, in turn, the upregulation of brain aromatase and ERalpha and ERbeta mRNA expression by MT at up to day 20 of age coincide with the period in which E(2) and MT have the maximal effect on gonadal feminization and masculinization, respectively.

Actins↗

Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome.

The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.

Adult↗

Differences in proteins synthesized by fibroblasts from normal individuals and patients with complete testicular feminization.

Patterns of protein synthesis by genital skin fibroblasts from three unrelated normal individuals and three unrelated patients with complete testicular feminization were compared to two-dimensional gel electrophoresis. cell lines were maintained in monolayer culture and pulse labeled with [35S]methionine. Cells were lysed in 9 M urea, and aliquots of 20 microliters subjected to isoelectric focussing and polyacrylamide gel electrophoresis followed by autoradiography. Gels of control fibroblasts showed two proteins (mol wt approximately 45,000, approximately 85,000; pKi approximately 5.0) markedly more prominent than on gels from affected fibroblasts. This pattern was unaltered by prior exposure to dihydrotestosterone, suggesting differences in constitutive proteins of the fibroblast cells. Parallel studies demonstrated a marked reduction in the ability of fibroblasts from patients with complete testicular feminization to bind androgens in vitro compared with those of normal individuals. The relationship between these proteins, androgen receptors, and androgen insensitivity requires further investigation.

Androgen-Insensitivity Syndrome↗

Power and feminism: a nursing science perspective.

Nurse executives are in an influential position to engineer health care reform and service delivery if their resources are fully maximized. Derived from Rogers' science and Barrett's power theory, this exploratory study demonstrated a weak relationship between power and feminism in female nurse executives, yet showed a modest correlation between feminism and the power subscale, freedom to act intentionally. Suggestions are provided for further development of the theoretical foundations of a nursing science perspective for nursing administration.

Adult↗

Growth hormone-secretory patterns in androgen-resistant (testicular feminized) rats.

To investigate the role of androgen receptors in the expression of the male GH-secretory pattern in adult rats, the GH-secretory patterns in androgen-resistant (testicular feminized) rats were compared with their normal male and female littermates. All animals were prepared with intraatrial Silastic catheters and bled every 15 min for 8 h (0800-1600 h). Normal male littermates displayed a characteristic low frequency, high amplitude pattern of GH secretion with bursts of GH occurring every 2.5-3 h and separated by prolonged trough periods where GH values remained low or undetectable (less than 5 ng/ml) for 45-90 min. Normal female littermates showed a characteristic high frequency, low amplitude pattern of GH secretion with pulses of GH occurring every hour. Compared to normal male littermates, females had lower individual GH peak amplitudes and shortened GH-trough periods which contain higher GH levels. GH-secretory profiles displayed by testicular-feminized animals qualitatively and quantitatively resembled those of the normal female littermates. These data suggest that androgen receptors are necessary for the expression of masculine GH-secretory patterns.

Age Factors↗

Gonadotropin-releasing hormone-stimulated luteinizing hormone secretion by perifused pituitary cells from normal, gonadectomized, and testicular feminized rats.

To elucidate further the manner in which gonadal steroids influence the secretion of LH, we examined the effects of gonadectomy and the absence of functional androgen receptors on GnRH-induced LH release from dispersed rat anterior pituitary cells. Intact and gonadectomized (GNX) normal rats and androgen-resistant, testicular feminized (Tfm) animals from the King x Holtzman strain (a mutant strain that possesses defective androgen receptors) were used. Dispersed pituitary cells were perifused with Medium 199 during a 4-h equilibration period and then subjected to eight 2.5-min pulses of GnRH introduced at 30-min intervals at concentrations ranging from 0.03-100 nM. Basal LH secretion by cells from intact male and female rats was indistinguishable (P = 0.79) and was substantially lower (P less than 0.0001) than that by cells from GNX male and female animals. Basal LH secretion by cells from Tfm rats was significantly higher (P less than 0.01) than that by cells from intact animals, but lower (P less than 0.005) than that by cells from GNX animals. In response to GnRH, perifused pituitary cells from animals representing all experimental groups demonstrated concentration-dependent LH release. Pituitary cells from intact female rats showed an overall greater (P less than 0.05) response to GnRH than cells from intact male rats. Pituitary cells from Tfm rats demonstrated a greater GnRH-stimulated LH mean response than cells from intact male (P less than 0.0001) or intact female (P less than 0.0001) rats. Gonadectomy of male rats resulted in an overall GnRH-stimulated LH release similar to that exhibited by cells from gonadectomized female rats (P = 0.61). Cells from Tfm animals released more LH in response to GnRH than those from gonadectomized male and female rats (P less than 0.001). These data demonstrate that the release of LH in response to GnRH by pituitary cells from intact male rats (i.e. in the presence of androgen and functional androgen receptors) is less than that seen by cells from intact females rats. Since circulating levels of testosterone and estradiol are known to be elevated in the testicular feminized rat, the heightened GnRH-stimulated LH release by cells from such animals may reflect either the long term lack of androgenic influence and/or the combined effects of androgen resistance and elevated levels of circulating estrogens.

Androgen-Insensitivity Syndrome↗

Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein.

The most severe form of congenital adrenal hyperplasia (CAH) is lipoid CAH. It was once thought that this disease was due to mutations in the cholesterol side-chain cleavage enzyme system, thus eliminating the ability to convert cholesterol to pregnenolone, causing a complete absence of steroid hormone production. We recently showed that lipoid CAH is due to mutations in the steroidogenic acute regulatory (StAR) protein, thus preventing acutely stimulated adrenal and gonadal responses to tropic stimulation. However, this lesion may permit low levels of StAR-independent steroidogenesis to persist until the accumulation of intracellular lipid deposits destroys steroidogenic capacity. This model would predict that the steroidogenic cells of the ovaries of affected 46,XX females should remain undamaged until puberty, at which time low levels of StAR-independent estrogen biosynthesis should be detectable. We describe a 15.5-yr-old 46,XX female with a classic history of lipoid CAH who underwent spontaneous feminization and cyclical vaginal bleeding beginning at age 13. Genetic analysis of the patient and her parents showed that she was homozygous for the novel StAR frameshift mutation 261delT. This is the first adolescent female with lipoid CAH who has undergone spontaneous feminization and who has been analyzed genetically. Finding an inactive StAR gene in this patient confirms our two-hit model of the pathogenesis of lipoid CAH, in which loss of StAR activity initially preserves StAR-independent steroidogenesis, which is lost only after cells undergo chronic tropic stimulation and subsequent damage from accumulation of cholesterol esters.

Adolescent↗

Aromatase p450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty.

A 7-yr-old girl presented with isosexual precocious puberty secondary to a feminizing adrenal adenoma. The adrenal tumor was found to express aromatase messenger ribonucleic acid. Enzyme kinetic studies revealed a high level of aromatase activity in the adrenal tumor, with a K(m) of 45 nmol/L and a maximum velocity of 25.6 pmol/mg.h. Aromatase activity was approximately 500-fold higher in the tumor than in adjacent normal adrenal tissue. Although histopathological examination of the tumor was most consistent with a benign adenoma, the aromatase transcripts present in the tumor corresponded to those previously associated with malignant as well as benign tumors. We consider the pattern of aromatase expression sufficient to warrant continued follow-up for tumor recurrence. Our case demonstrates that isosexual precocious puberty secondary to a feminizing adrenal tumor can be due to estrogen synthesis from the tumor itself rather than peripheral aromatization as had been previously theorized.

Adenoma↗

Consequences of feminization of a profession: the case of Canadian pharmacy.

Although the influx of women into formerly entirely male-dominated professions has attracted much commentary from members of these professions, little investigation of the consequences of rapid, large-scale feminization has been undertaken for particular professions. The results of a pilot study in Canadian pharmacy suggest that fears of shortages due to women working part-time while they raise their children, are unfounded. However, our survey results suggest that women are differentially drawn into pharmacies run by corporations rather than independent businesses. This may allow them to reorient pharmacy away from its business base and towards its chosen new professional jurisdiction of counselling. On the other hand, the demise of independent pharmacy, that traditionally attracted males, may bring with it less control by pharmacists over what they do in everyday practice. The possibility that similar processes are operating in other feminizing professions with entrepreneurial components, such as dentistry and optometry, should be investigated.

Canada↗

Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model.

UNLABELLED: The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation. INTRODUCTION: Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance. MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover. RESULTS: As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice. CONCLUSIONS: These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.

Androgen-Insensitivity Syndrome↗

[Feminizing genitoplasty and congenital adrenal hyperplasia: analysis of anatomical results].

OBJECTIVE: To evaluate the anatomical and cosmetic results of feminizing genitoplasty in girls with ambiguous genitalia due to Congenital Adrenal Hyperplasia (CAH). CASUISTIC AND METHOD: Twenty-seven females with genital ambiguity (Prader III-V) due to CAH underwent an one-stage feminizing genitoplasty and were followed for a mean time of 4 years. In twelve girls, two cutaneous labioscrotal island-flaps were associated with the conventional genitoplasty, to decrease the excess of labia majora and to enlarge the vaginal introitus. Urinary tract infections were observed in sixteen girls in the preoperative and in only seven in the postoperative period. The cosmetic results were obtained by the systematic anatomical evaluation of the different structures that compose the genitalia. RESULTS: The results of clitoroplasty were considered good in 63% of the cases; however, 4 girls developed clitoral atrophy. An excess of labia majora was present in 25% and persistence of the urogenital sinus occurred in 11% (three children without labioscrotal island flap). The labioscrotal island flap was considered technically feasible and reproducible. Five girls had to be re-operated. The cosmetic results were considered excellent or good in 63% of the cases, satisfactory in 18.5% and unsatisfactory or bad in 18.5%. CONCLUSIONS: The anatomical and cosmetic results were good in majority of the cases; however, some technical aspects should be adjusted, to avoid irreversible sequels and re-operations.

Adrenal Hyperplasia, Congenital↗