Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 32-yr-old man with a history of hypospadias, unilateral cryptorchidism, and pubertal gynecomastia (all surgically corrected) presented with complaints of infertility. Examination revealed scant virilization, recurrence of gynecomastia, small but normal sized testes, small prostate, and oligospermia. His plasma LH, testosterone, dihydrotestosterone, and estradiol levels were high, and his plasma FSH was below the reference range of adult men. An assay of pubic skin fibroblast androgen receptors confirmed the diagnosis of a form of incomplete androgen insensitivity syndrome. Administration of the estrogen receptor antagonist tamoxifen (10 mg, twice daily) induced an increase in plasma FSH greater than that which occurred in six men with idiopathic oligospermia. This man's wife conceived three times during a period of 5 yr, each time after he had received tamoxifen for 12-20 weeks and had considerable improvement of sperm parameters. Conversely, upon cessation of tamoxifen therapy, the semen abnormalities returned. These results indicate that estrogen action impaired this man's fertility, and the impairment could be reversed by administration of an estrogen receptor antagonist.
 ...
PMID:Improvement of spermatogenesis after treatment with the antiestrogen tamoxifen in a man with the incomplete androgen insensitivity syndrome. 256 21

A prospective randomized trial of tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer was conducted from December 1980 to September 1985. Patients were eligible regardless of site of disease, estrogen receptor status, or age. Sixty-two of sixty-three randomized patients were evaluable for response. Overall response for tamoxifen and fluoxymesterone was 11% with 61% stabilization of disease, versus 12% response rate for tamoxifen and danazol with 59% stabilization. Toxicities with tamoxifen and fluoxymesterone were greater with an increase in masculinization. We conclude that the response rates to the combinations of tamoxifen and fluoxymesterone or tamoxifen and danazol reported are equivalent in this study but that the increased toxicity with tamoxifen and fluoxymesterone would make tamoxifen and danazol the treatment of choice if a combination were to be used.
 ...
PMID:Tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer--a randomized study. 305 38

17 cases of peristant pubertal gynecomastia (which differs from physiologic breast enlargement by their volume and duration) were studied. Plasma estrogens and urinary phenol steroids excretion were found higher than in normal boys. The main biological finding in these subjects was a decrease of the plasma testosterone/estradiol ratio, and a moderate but transient increase in plasma prolactin. LH and FSH were within the normal range. In the mammary tissue, no estrogen receptor was detectable and aromatase activity was in the same range as in adipose tissue. Pathological examination showed a simulataneous proliferation of galactophoric and fibroblastic stroma. Thus, persistant pubertal gynecomastia could be related to an elevated sensitivity of the mammary tissue to a moderate increase of plasma estrogens. Such a sensitivity could be due to an insufficient masculinization of the mammary anlage during the intra-uterine life.
 ...
PMID:[Persistant pubertal gynecomastia. Biological study (author's transl)]. 625 3

The present review focuses on some aspects of the function of catechol-O-methyl-transferase (COMT) in the hypothalamic control of gonadotrophin release by the pituitary gland. The in situ influence of a catecholestrogen (2 OH.E2) on the amount of COMT in the hypothalamic nuclei involved in such control as well as on the process of sexual differentiation of the brain is also discussed. Catecholestrogens do not play a significant role in the induction of sexual differentiation and the observed action is probably a pharmacological one. It is difficult to understand why a substance whose structure is so closely related to that of estrogen is so much less active. Most probably the estrogen receptor in the cytosol at this stage of development is not able to recognize the catecholestrogen. Since catecholestrogens are not true virilizing substances they may be used to assess the critical levels of enzymes which are required to determine the sexual pattern of hypothalamic activity. The fact that the extent of the changes in COMT content of the hypothalamus is related to the amount of hormone used to induce virilization strengthens the view that sexual differentiation is the consequence of a genomic change during the critical period, which will induce an enzymatic pattern characteristic of the male acyclic pattern of gonadotrophin control. The finding that the COMT content of the hippocampus also changes in parallel to sexual differentiation leads us to speculate that perhaps sexual behavior may also be differentiated in the same way.
 ...
PMID:Hypothalamic nuclei catechol-O-methyl-transferase and the process of brain sexual differentiation. 651 34

Prenatal stress in rats has been found to alter the sexual dimorphism of brain structures and the sexual behavior of male offspring, pointing to an impaired masculinization of the brain during the perinatal period of brain sexual differentiation. Masculinization of the brain depends on the presence during this critical period of three main elements: adequate levels of testosterone, aromatase activity (locally converting testosterone to estradiol), and brain estrogen receptor (ER) density. In the present study, we measured by reverse transcription-polymerase chain reaction (RT-PCR) the levels of ER messenger RNA (mRNA) expression in the hypothalamus of either prenatally-stressed or control male rats at postnatal (P) days 3, 12 and 90. During the early postnatal period (P3), hypothalamic ER mRNA expression was higher in prenatally stressed male rats (6.12 +/- 0.37) than in controls (4.51 +/- 0.55) (P = 0.015). This difference was not, however, found at a later developmental stage (P12, 5.39 +/- 0.65 versus 5.39 +/- 0.47) or in adult animals (P90, 6.79 +/- 1.55 versus 7.07 +/- 1.11). This transient elevation of hypothalamic ER mRNA expression resembles the developmental profile of ER mRNA in females. These observations support the idea that androgens play a pivotal role in the demasculinization process, and suggest that testosterone production or aromatization is reduced in prenatally-stressed males during the perinatal period of sexual differentiation, leading to a transient upregulation of unstimulated estrogen receptors.
 ...
PMID:Transient neonatal elevation in hypothalamic estrogen receptor mRNA in prenatally-stressed male rats. 890 3

Effects of gene products on reproductive behavior which are relatively direct include those of the estrogen receptor and progesterone receptor. For example, work with estrogen receptor-deficient (ERKO) female mice has extended previous evidence contributing to the neurochemical analysis of lordosis behavior. On the other hand, sex differences in behavior present a classic example of indirect effects of genes on behavior. Work with ERKO male mice shows the necessity of ER gene expression for normal masculinization of the brain. In particular, behavioral assay results distinguish apparent motivational performance of ERKO males from male mating reflexes: the former is similar to that of wild-type males in important respects, while the latter are deficient in ERKO males. The present paper first reviews a small number of clear genetic contributions to reproductive behaviors, and then reports one experiment pertinent to the interpretation of the behavioral status of ERKO male mice.
 ...
PMID:Reproductive functions illustrating direct and indirect effects of genes on behavior. 904 73

The distribution of the neuronal nitric oxide synthase (nNOS), androgen receptor (AR), estrogen receptor (ER) and aromatase (ARO) was studied in the dorsal and ventral premammillary nuclei (PMd and PMv) of the newborn rat by immunohistochemistry. In the intact male pups, nNOS immunoreactivity (-IR) was present both in the PMd and the PMv, while AR-IR was detected only in the PMv. On the other hand, ER-IR and ARO-IR were scarcely encountered in the both PMd and PMv. By double immunostaining of nNOS and AR, all the nNOS-IR cells in the PMv were revealed to contain AR-IR. In the intact female pups, nNOS-IR was present in the both PMd and PMv, but neither ER-, nor ARO-IR were detected in the PM region. In the PMv of the intact female rat, no AR-IR was detected at 6 days of age, while it was detected as only a faint staining within 12 h after birth. When the male pups were castrated neonatally, no AR-IR was detected in the PMv. Subcutaneous injections of 5alpha-dihydrotestosterone (DHT) induced strong AR-IR in the castrated male and the intact female pups. On the contrary, the intensity of nNOS-IR stayed unchanged among these animals. Neonatal androgen and nitric oxide has been considered important to brain development. Moreover, involvement of the PMv in aggressive and mating behavior of male animals has been reported. Together with the fact that the AR-IR and nNOS-IR were found in the same neurons in the PMv, involvement of this nucleus in masculinization of the brain by non-aromatizable androgen is postulated.
 ...
PMID:Co-localization of androgen receptor and nitric oxide synthase in the ventral premammillary nucleus of the newborn rat: an immunohistochemical study. 912 76

The goals of this presentation are to review the essential roles of aromatase, estrogens and the estrogen receptor in pubertal growth. Estrogen deficiency due to mutations in the aromatase gene (CYP19) and estrogen resistance due to disruptive mutations in the estrogen receptor gene have no effect on normal male sexual maturation in puberty. However, they lead to absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, continued growth into adulthood and very tall adult stature in both sexes. Gonadotropin and androgen levels are elevated in patients with either estrogen deficiency (aromatase deficiency) or estrogen resistance (estrogen receptor mutation). Glucose intolerance, hyperinsulinemia and lipid abnormalities are also present. Skeletal integrity is compromised. Increased bone turnover, reduced bone mineral density and osteoporosis develop in both sexes. Sexual orientation is appropriate in males and females. In females, aromatase deficiency in the ovary causes pubertal virilization and multicystic ovaries because of elevated gonadotropins and androgens. Simultaneously, secondary sexual maturation fails to occur. Placental aromatase deficiency results in virilization of the mother and her female fetus because of the accumulation of potent androgens which are not converted to estrogens. The male fetus has normal genitalia. In conclusion, estrogens are essential for normal female secondary sexual maturation, bone maturation, epiphyseal fusion, pubertal growth spurt and achievement of normal bone mineral mass. Estrogens also influence insulin sensitivity and lipid homeostasis. However, estrogens do not appear to be essential for fetal survival, placental growth, or female sexual differentiation.
 ...
PMID:Pediatric endocrinology update: an overview. The essential roles of estrogens in pubertal growth, epiphyseal fusion and bone turnover: lessons from mutations in the genes for aromatase and the estrogen receptor. 955 63

The role of the a form of estrogen receptor (ER alpha) gene expression in the regulation of testosterone-dependent male reproductive behaviors was investigated using ER knockout mice (ERKO), which are specifically deficient in functional ER alpha, but not ER beta, gene expression. Previous studies in gonadally intact ERKO mice revealed that male aggressive behavior was greatly reduced by the lack of a functional ER alpha gene. In the present study the almost complete suppression of male-typical offensive attacks was further confirmed in ERKO mice that had been singly housed since weaning. Regarding aggression, it was also found that ER alpha gene disruption virtually abolished the propensity to initiate offensive attacks, even though ERKO mice could elicit attacks from resident C57BL/6J mice as wild-type (WT) and heterozygous littermates. Daily injection of testosterone propionate (TP) was completely ineffective in inducing aggressive behavior in gonadectomized ERKO mice, whereas it successfully restored aggression in WT mice. In contrast, male sexual behaviors, mounts and intromissions, were induced by daily injection of TP in both gonadectomized ERKO and WT mice. In addition to TP, dihydrotestosterone propionate (DHTP) was also effective in restoring mounts in ERKO mice, although DHTP was much more potent in WT mice than in ERKO mice. Neither TP nor DHTP, however, ever induced ejaculation in ERKO mice. These results together with previous findings in gonadally intact ERKO mice suggest that ER alpha may be responsible for the regulation by testosterone of consummatory, but not motivational, aspects of male sexual behavior. Finally, ERKO male mice retrieved newborn pups placed in their home cage with similar latencies to males of the two other genotypes. During parental behavior tests, however, a higher percentage of ERKO mice (70%) showed infanticide compared with WT mice (35%). The latter result was interpreted as showing that ER alpha activation by testosterone during the perinatal period may exert a suppressive effect on testosterone-inducible infanticide in adulthood. With respect to three major testosterone-dependent behavioral systems reflecting masculinization, these findings demonstrate three different types of effects due to ER alpha gene disruption.
 ...
PMID:Modifications of testosterone-dependent behaviors by estrogen receptor-alpha gene disruption in male mice. 983 45

In order to study the physiological implication of sex steroid hormones in gonadal sex differentiation in fish, we first investigated the potential role of estrogens using two fish models: the rainbow trout (Oncorhynchus mykiss) and a tilapia species (Oreochromis niloticus). All experiments were carried out on genetically all-male (XY) and all-female (XX) populations. In vivo treatments with an aromatase inhibitor (ATD, 1,4,6- androstatriene-3-17-dione) result in 100% masculinization of an all-female population in rainbow trout (dosage 50 mg/kg of food) and 75.3% in tilapia (dosage 150 mg/kg of food). In tilapia, the effectiveness of the aromatase inhibition by ATD is demonstrated by the marked decrease of the gonadal aromatase activity in treated animals versus control. No masculinization is obtained following treatment with an estrogen receptor antagonist (tamoxifen) in both species. Aromatase and estrogen receptor gene expression was studied in rainbow trout by semi-quantitative RT-PCR in gonads sampled before, during and after sex-differentiation. Aromatase mRNA is specifically detected in female gonads, 3 weeks before the first sign of histological sex-differentiation, i.e., first female meiosis. Aromatase expression in male gonads is at least a few hundred times less than in female gonads. Estrogen receptor gene is expressed in both male and female gonads at all stages with no dimorphic expression between sexes. Specific aromatase gene expression before ovarian differentiation was also demonstrated using virtual Northern blot, with no expression detected in male differentiating gonads. From these results it can be concluded that estrogen synthesis is crucial for ovarian differentiation, and transcription of the aromatase gene can be proposed as a key step in that process in fish.
 ...
PMID:Involvement of estrogens in the process of sex differentiation in two fish species: the rainbow trout (Oncorhynchus mykiss) and a tilapia (Oreochromis niloticus). 1047 75


1 2 3 4 Next >>