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PubMed2001

Characterization of mutations that feminize gametophytes of the fern Ceratopteris.

Gametophytes of the fern Ceratopteris are either male or hermaphroditic. Their sex is epigenetically determined by the pheromone antheridiogen, which is secreted by the hermaphrodite and induces male and represses female development in other young, sexually undetermined gametophytes. To understand how antheridiogen represses the development of female traits at the genetic level, 16 new mutations that feminize the gametophyte in the presence of antheridiogen were identified and characterized. Seven are very tightly linked to the FEM1 locus previously described. Nine others define another locus named NOTCHLESS1 (NOT1), as several of the not1 mutants lack a meristem notch. Some not1 mutations also affect sporophyte development only when homozygous, indicating that the not1 mutations are recessive and that NOT1 is also required for normal sporophyte development. The epistatic interactions among FEM1, NOT1, and other sex-determining genes are described. This information was used to expand the genetic model of the sex-determining pathway in Ceratopteris. On the basis of this model, we can say that the presence of antheridiogen leads to the activation of the FEM1 gene, which not only promotes the differentiation of male traits, but also represses female development by activating the NOT1 gene. NOT1 represses the TRA genes necessary for the development of female traits in the gametophyte.

Crosses, Genetic↗
PubMed1991

A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse.

The testicular feminized (Tfm) mouse lacks completely androgen responsiveness; and therefore, is unique for studying the role of androgenic steroids in different biological processes. In order to understand the molecular basis of this mutation, 2.8 kilobases of cDNA encoding the Tfm mouse androgen receptor (AR) were amplified with a polymerase chain reaction (PCR) technique. No large deletion in the coding region of the Tfm mouse AR was detected. However, sequence analysis revealed a single base deletion in the coding region of the Tfm AR mRNA. This mutation, which is located in the amino-terminus domain of the receptor, is predicted to cause a frame-shift in translation resulting in a premature termination of AR synthesis at amino acid 412. In vitro translation studies of the recombinant wild type and Tfm AR's demonstrated that the Tfm AR cDNA failed to produce a full-length receptor. Furthermore, the Tfm AR was demonstrated to lack transcriptional activation capability by cotransfection experiments using the Tfm AR with a reporter plasmid of mouse mammary tumor virus long terminal repeat linked to the chloramphenicol acetyltransferase gene. These studies provide evidence of the molecular defect which causes androgen insensitivity in the Tfm mouse.

Amino Acid Sequence↗
PubMed1981

Induction of various androgen-dependent esteroproteases (trypsin-like and chymotrypsin-like enzymes) by tri-iodo-L-thyronine in the submandibular glands of female mice and mice with testicular feminization.

Trypsin-like and chymotrypsin-like esteroprotease isozymes of the mouse submandibular gland were separated by isoelectric focusing. In normal female mice the following pI-isozyme activities were found; pI-4.6, -5.6 (shoulder), -5.8, -7.1, and -9.9, hydrolytic activities for benzoylarginine ethylester (BAEE) (trypsin-like enzymes), and pI-4.7 and -10.3 hydrolytic activities for acetyltyrosine ethylester (ATEE) (chymotrypsin-like enzymes). In mice with testicular feminization (Tfm mice), only pI4.6 hydrolytic activity for BAEE was found; no ATEE hydrolytic activity was detected. In normal female mice, both 5 alpha-dihydrotestosterone (5 alpha-DHT) and tri-iodo-L-thyronine (T3) significantly increased all these isozymes except the pI-4.6 hydrolytic activity for BAEE. In Tfm mice, T3 also increased all these isozymes except the pI-4.6 hydrolytic activity for BAEE, but 5 alpha-DHT had no effect on any enzymes. These results suggest that the pI-4.6 hydrolytic activity for BAEE is non-inducible by the two hormones. Androgen does not seem to be involved in the inductions of these esteroproteases by T3.

Androgen-Insensitivity Syndrome↗
PubMed1981

Induction of epidermal growth factor by tri-iodo-L-thyronine in the submandibular glands of mice with testicular feminization.

The content of epidermal growth factor (EGF) as a high molecular weight complex (HMW-EGF) in the submandibular glands of mice was measured simply by a single radial immunodiffusion method. In female mice, the amount of HMW-EGF was increased 10-fold by tri-iodo-L-thyronine (T3) and 60-fold by 5 alpha-dihydrotestosterone (5 alpha-DHT). In mice with testicular feminization (Tfm), which are genetically deficient in androgen receptor, T3 but not 5 alpha-DHT increased the HMW-EGF from a non-detectable level to 5.4 +/- 0.94 micrograms/mg protein. It was concluded that EGF is also synthesized under the control of thyroid hormone in vivo, and that androgen was not involved in this induction of EGF by thyroid hormone.

Androgen-Insensitivity Syndrome↗
PubMedDate not supplied

Mandible shape analysis in a testicular feminization (Tfm) strain of mice.

The role of androgens on the sexual dimorphism of mandible shape was investigated in mice carrying the X-linked gene for testicular feminization (Tfm), which is known to determine a profound insensitivity to testosterone and is associated with a severe reduction in androgen receptor levels in Tfm/Y males. Mandible shape analysis in an inbred strain of mice segregating for the Ta (tabby) and Tfm mutations showed that the sexual dimorphism observed between +Ta/+Ta females and +Ta/Y males almost disappeared between Tfm+/+Ta females and Tfm+/Y males. In addition, a canonical discriminant analysis showed that these two closely related classes, Tfm+/+Ta and Tfm+/Y, are readily differentiated from both the +Ta/+Ta and +Ta/Y classes. These results suggest that androgens are involved in the mandible shape sexual dimorphism and play a role in mandibular development in both males and females.

Analysis of Variance↗
PubMed2002

Suitable and remunerative employment: the feminization of hospital dispensing in late nineteenth-century England.

This article looks at the contingent developments that led to the feminization of hospital dispensing at the end of the nineteenth century in England. In the 1870s, as a result of the campaign of the Women's Movement to open medicine to women, the Society for Promoting the Employment of Women found it possible to place some of its protégées in the dispensaries of hospitals founded by members of the Movement. Coincidentally, a radical member of the Council of the Pharmaceutical Society smoothed the way for them to take the Society's examinations, thus setting up an expectation that these women should be qualified. By the 1880s, the practice of employing female dispensers had spread to Birmingham, and the women here adopted a less difficult and expensive qualification, the Apothcaries' Assistant's Certificate, as the qualification of choice. The 1890s also saw increasing pressure on mainstream hospital dispensaries to replace the untrained assistants in their dispensaries, customarily employed on the Babbage Principle to save money, with qualified ones. In consequence, hospital managements sought a new means of containing costs and, turning to the kind of women already shown to be competent in Women's Movement hospitals, found the solution in a vertical gender-segregation, where the lesser qualification of women dispensers made them 'unpromotable' to head dispenser, thus preserving the career ladder for more highly-qualified male dispensers.

History of Pharmacy↗
PubMed2004

Putative homeodomain transcription factor 1 interacts with the feminization factor homolog fem1b in male germ cells.

The Phtf1 gene encodes a membrane protein abundantly expressed in male germinal cells. Using a two-hybrid screening procedure we have identified FEM1B, an ortholog of the C. elegans feminization factor 1 (FEM-1), as a binding partner for PHTF1. We studied FEM1B expression in the rodent testis and found that Fem1b mRNA is present at high levels during meiosis and after, during spermiogenesis, in a similar manner to Phtf1 mRNA. Accordingly, Western blot and immunofluorescence revealed the presence of PHTF1 and FEM1B in the same cell types, and by coimmunoprecipitation we demonstrated the association between these proteins. We characterized some aspects of this interaction and showed that the ANK domain of FEM1B is necessary for the interaction with the amino extremity of PHTF1. Next, we found that FEM1B can bind several intracellular organelles and demonstrated that PHTF1 would recruit FEM1B to the endoplasmic reticulum membrane. Previous in vitro experiments had suggested that the human FEM1B was involved in apoptosis. After comparing expression profiles of FEM1B and PHTF1 with apoptotic events occurring in the normal seminiferous tubules, we suggest that neither FEM1B nor PHTF1 are directly implicated in apoptosis in this tissue.

Animals↗
PubMed1984

Characterization of androgen binding and deoxyribonucleic acid synthesis in prostate-like structures induced in the urothelium of testicular feminized (Tfm/Y) mice.

We have examined tissue recombinants composed of wild-type (rat or mouse) urogenital sinus mesenchyme plus adult testicular feminized (Tfm/y) bladder epithelium for the autoradiographic localization of androgen binding. In the presence of androgens, wild-type mesenchyme reprogrammed the androgen-insensitive bladder epithelium to undergo prostatic morphogenesis. Steroid autoradiography of [3H] dihydrotestosterone or [3H] methyltrienolone binding in these recombinants, however, showed that the ligands were specifically bound only in the nuclei of stromal cells, indicating that the effects of androgens on prostatic morphogenesis are mediated by the mesenchyme. Furthermore, autoradiograms prepared from recombinants that were exposed to [3H] thymidine showed that the generation of prostatic form required a specific, androgen-induced proliferation in the androgen-insensitive bladder epithelium. The significance of these data in relation to epithelial-stromal interactions occurring during prostate development is discussed.

Androgen-Insensitivity Syndrome↗
PubMedDate not supplied

Regulation of gonadotropin response in testicular feminization syndrome.

The effects of hormonal manipulation on gonadotropin, androgen, and estrogen concentrations in a patient with testicular feminization syndrome (TFS) were studied to clarify the feedback regulation of gonadotropins. Baseline serum LH concentrations were normal to high and FSH concentrations were normal despite markedly elevated plasma testosterone concentrations, implying the lack of a reciprocal control relationship, and fluoxymesterone administration failed to alter gonadotropin or androgenic steroid levels. Clomiphene administration resulted in a rise in both LH and androgen levels, while moderate doses of exogenous estrogens effected a diminution in testosterone but did not significantly alter the levels of gonadotropins. Following gonadectomy, these same doses of estrogens produced a dramatic fall in the very high postoperative levels of gonadotropins. These results suggest that gonadotropin regulation is mediated by estrogens and not directly by androgens in TFS.

Adult↗
PubMed1984

Computed tomography of testicular feminization.

Testicular feminization is a rare genetic disease characterized by an XY karyotype, bilateral functional testes, female external genitalia, blind vagina, and absence of müllerian derivatives. The presurgical localization of the testes is critical and is particularly well suited to the cross-sectional imaging capability of CT.

Adolescent↗
PubMedDate not supplied

Testicular feminization: role of MRI in diagnosing this rare male pseudohermaphroditism.

PURPOSE: The purpose of our study was to assess the role of MR in the diagnosis and follow-up of patients with testicular feminization (TF). METHOD: MR scans of seven patients with TF were retrospectively reviewed. RESULTS: MR could diagnose uterus agenesis in all cases. Undescended testes were depicted within or just below the inguinal canal in four cases. They were smaller and more hypointense than those in normal males. Testes that we could not find by MR were found during surgery in two cases. They were just below the inguinal canal where we had not scanned caudally enough in one and they were too small to be detected in the other. CONCLUSION: MR can demonstrate both uterine agenesis and undescended testes in TF. The latter tend to be missed because they are small and can be anywhere in the abdomen and inguinal canal. Radiologists should perform careful MR examination to detect testes in patients suspected having TF, as these organs are more likely to undergo malignant neoplasia.

Adolescent↗
PubMed1995

Measurement of pudendal evoked potentials during feminizing genitoplasty: technique and applications.

We report on 6 patients (average age 13 months) with ambiguous genitalia who underwent stimulation of the dorsal neurovascular bundle of the phallus during feminizing genitoplasty. Three patients had the adrenogenital syndrome, 1 underwent removal of a masculinizing adrenal tumor before genital reconstruction, 1 had mixed gonadal dysgenesis and 1 had male pseudohermaphroditism. Stimulation of the dorsal neurovascular bundle with measurement of electromyographic nerve conduction latencies was performed before and after ligation of the corporeal bodies and excision of the erectile tissue. In all 6 cases electromyographic responses were preserved after phallic reduction. Our study clearly shows that modern techniques of genital reconstruction allow for preservation of nerve conduction in the dorsal neurovascular bundle and may permit normal sexual function in adulthood.

Clitoris↗
PubMedDate not supplied

Physician gender and primary care patient satisfaction: no evidence of "feminization".

BACKGROUND: Observers predict that the influx of women into the medical profession will alter the way in which medicine is practiced, incorporating more "feminine" values of caring, listening to patients, and patient centeredness, in contrast to the "masculine" values of curing, dictating to patients, and care provider centeredness. Consequently, patient satisfaction with medical care will improve. SUBJECTS AND METHODS: Retrospective database analysis of satisfaction survey data. A total of 3985 surveys from primary care patients were examined after having identified the gender of the patient's physician. Ten survey items that pertained to physician attributes were analyzed, individually and in the aggregate, in a series of 2 x 2 analyses of covariance, with physician gender and patient gender serving as independent variables, and patient age and the overall level of patient satisfaction from the physician's facility serving as covariates. An additional analysis of covariance, with the same independent variables and covariates, examined patients expressed likelihood of recommending their physician to others. RESULTS AND CONCLUSIONS: There were no main or interaction effects for physician gender or patient gender after adjusting for patient age and facility-level satisfaction. The implications of these results for the "feminization" hypothesis are discussed.

Cross-Sectional Studies↗
PubMed2005

New concepts in feminizing genitoplasty--is the Fortunoff flap obsolete?

PURPOSE: We retrospectively evaluated the results of an original technique that combines mobilization of the urogenital sinus with the creation of urogenital flaps to enlarge the vaginal introitus for 1-stage feminizing genitoplasty in children with urogenital sinus anomalies, thus, avoiding the use of posteriorly based perineal flaps. MATERIALS AND METHODS: A total of 11 patients with urogenital sinus anomalies have undergone a modified Fortunoff technique combining total urogenital mobilization with the creation of urogenital sinus flaps by a single surgeon (RG) since 1998. Patient age at surgery ranged from 3 months to 13 years (mean 3.8 years). Diagnoses included congenital adrenal hyperplasia in 7 patients, cloacal malformation in 2 and urogenital sinus malformation in 2. Eight patients underwent a perineal approach and 3 underwent a posterior sagittal approach. RESULTS: Followup ranged from 3 months to 5 years (mean 2.5 years). The cosmetic appearance was considered superior to that achieved with previous techniques. The vagina had a more physiological position in all patients except 1, and no patient had development of vaginal stenosis. One patient had development of a mild mid urethral stricture that required a single dilation using anesthesia. In this patient cystourethroscopy performed 3 years later was normal. CONCLUSIONS: We believe that the redundant urogenital sinus tissue must not be discarded, but rather incorporated into the reconstruction of the posterior vaginal wall, thus, avoiding the use of perineal skin flaps. This modification allows placement of the vaginal opening in a more physiological position with a better cosmetic appearance than previous techniques.

Adolescent↗
PubMed1977

Effects of a feminizing testicular Leydig cell tumour on nontumorous testicular tissue: an ultrastructual study.

The ultrastructural effects of a Leydig cell tumour of the testis on nontumorous testicular tissue have not yet been reported. Described here are the electron microscopic findings in the nonneoplastic testicular tissue of a patient with a feminizing testicular Leydig cell neoplasm. Serial studies were carried out over a period of 31/2 years prior to removal of the tumour. The overall general picture was characterized by progressive degeneration of Leydig cells, cells of the germinal series and Sertoli cells. Concomitantly, there was increasing thickening and fibrosis of the tubular walls. Cytoplasmic focal accumulations of glycogen, increasing with the duration of the disease, were conspicuous in many spermatogonia. All of these alterations are nonspecific and are attributable to adverse endocrine effects introduced by the oestrogen-secreting tumour. They were present bilaterally and were more prominent on the tumour-bearing side. Attention is drawn to the role of artifacts, fixation technique and degenerative processes in the production and appearance of certain ultrastructural findings, such as 'light' and 'dark' cells, myelin figures, membranous whorls and focal glycogen accumulations.

Adult↗
PubMed1980

LH/hCG responsive adenylyl cyclase in rat testis and testes from testicular feminized male (Tfm) rats and mice; desensitization by homologous hormone.

Testes of testicular feminized (tfm) rats and mice, as well as of normal male rats contain an LH/hCG responsive adenylyl cyclase. Basal, as well as hCG stimulated activities were higher in tfm rats and mice than in normal rats. The presence of an LH/hCG responsive adenylyl cyclase in the testis of tfm rats and mice shows that the greatly elevated LH levels present in males having this syndrome, giving 80-90% reduction in LH/hCG receptors, do not cause an uncoupling of the remaining receptors from the adenylyl cyclase. It also shows that androgens are not essential for coupling of the LH/hCG receptors to the adenylyl cyclase. Injection of 200 IU of hCG into adult normal rats and tfm rats caused, after 48 h, a complete loss of LH/hCG stimulated adenylyl cyclase whereas the FSH responsive adenylyl cyclase in both animal preparations was maintained. Desensitization of the LH responsive adenylyl cyclase by hCG in normal rats, confirms previous studies showing lack of hCG stimulated cyclic-AMP secretion after a comparable dose of hCG in vivo. Similarly, hCG (50 IU) caused a transient loss of LH/hCG responsive adenylyl cyclase in tfm mice, with a complete disappearance of response after 24 h. At 48 and 72 h after injection of hCG the response gradually returned to normal. The fact that hCG caused a complete desensitization of the LH/hCG responsive adenylyl cyclase in both tfm rats and mice, proves that androgen receptor mediated events are not involved in hCG desensitization of the adenylyl cyclase in Leydig cells.

Adenylyl Cyclases↗
PubMed1995

The feminization of the medical profession in Israel.

Two factors have caused major changes in the gender composition of the Israeli medical profession in recent years: (i) a wave of immigration from the former USSR, which increased the doctor population by approximately 70% and which included a majority of women physicians, and (ii) the entry of more Israeli women into medical school. This report presents the current gender status of the Israeli medical profession, regarding students and physicians, and the choice of medical specialty and academic seniority, and compares gender differences in Israel with those in other countries. Traditional patterns of specialization persist in Israel, with women still concentrated in primary care (family medicine, paediatrics and psychiatry). In addition, women still face obstacles in entering the more prestigious (mainly surgical) specialties. Whilst the number of women in academic medicine has increased over the last decade, women are still concentrated in the lowest echelons of academic medicine. However, the steady trend towards the feminization of medicine will inevitably lead to an increase of women in all areas of the medical profession. Because cross-cultural studies have repeatedly revealed that women doctors have a more humanistic and personalized approach to patient care, a higher ratio of women in the profession should have a qualitative effect in this direction, despite the bureaucratic and fiscal constraints incumbent upon practising doctors. As more women become role models for medical students, their approach will influence the education of the doctors of the future.

Career Choice↗
PubMed2004

Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization).

Graham Little-Piccardi-Lassueur syndrome is characterized by the presence of cicatricial alopecia on the scalp, keratosis pilaris in the skin of trunk and extremities, and non-cicatricial hair loss in pubis and axillae. A frequent form of male pseudohermaphroditism is complete androgen insensitivity syndrome (CAIS), also known as testicular feminization syndrome. It refers to genetic males with XY karyotype who, owing to a lack of sensitivity in the peripheral androgenic receptors, develop a female phenotype. Axillary and pubic hair is typically scarce or absent. To our knowledge, this is the first case describing the association of the two processes. The presence of both processes in the same patient furthers our understanding of Graham Little-Piccardi-Lassueur syndrome as it rejects the influence of androgens in the alopecias accompanying this syndrome. The coincidence of non-cicatricial alopecia in axillary and pubic hair in both processes is also remarkable.

Adult↗