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

The effect of pinealectomy (PX) and sham-pinealectomy (SPX) on the calculated concentration of NaCl in the total volume of fluid drunk per day ([NaCl]I) in female rats offered a free choice between water and 3% NaCl solution was measured. In normal rats the [NaCl]I increases after attainment of sexual maturity. The increase can be accelerated by neonatal PX. Neonatal 'masculinization' of female rats by testosterone propionate (TP2) removes the increase of [NaCl]I in adult females and suppresses the acceleration due to PX. Neonatal SPX interferes with this decreasing effect of TP2 in adult female rats. The role of the pineal gland in the regulation of water and salt intake is discussed in relation to sex differences, sexual maturation and neonatal stress.
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PMID:The pineal gland and the effect of neonatal administration of androgen upon the development of spontaneous salt and water intake in female rats. 116 47

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. The development of sensory motor behaviour and emotional reactions was delayed by 1-2 days in the prenatally ethanol exposed pups as assessed by tests on body righting, acoustic startle response, air righting, rearing and ultrasonic vocalization. In the open-field test the normally occurring behavioural difference between the sexes was not found in the prenatally ethanol exposed pups. Both sexes of the ethanol exposed pups behaved like the female controls suggesting deficient masculinization of the ethanol exposed male pups during foetal age. Biochemical analysis of the brains showed a decreased synthesis of serotonin and dopamine.
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PMID:Effects of maternal ethanol consumption on the offspring sensory-motor development, ultrasonic vocalization, audiogenic immobility reaction and brain monoamine synthesis. 286 19

Data were collected from intact males, castrated males and ewe lambs to investigate the effect of presence or absence of testosterone prenatally and during the postweaning period on postweaning growth, feed intake and carcass chemical composition. Half the lambs from each sex were the progeny of dams that had received five injections of testosterone cyprionate from d 32 through d 87 of gestation. Linear contrasts were used to detect differences. Postweaning daily gain of intact males was greater (P less than .01) than that of male castrates. Ewe lambs from treated dams had approximately 12% greater rate of growth (P less than .04) than ewe lambs from control dams. Ewe lambs from dams that had been treated were 28% more efficient (P less than .01) in the conversion of food to weight than those from untreated dams. Ewe lambs from treated dams had heavier livers (P less than .07). Carcass protein for intact males was greater (P less than .11) than for castrates, and extractable fat was less (P less than .05). Masculinization of growth characteristics of ewe lambs affected the quantity of carcass fat relative to control ewes (7.59 vs 8.92 kg). These ewe lambs also had more water in the carcass than did the control ewes (13.93 vs 12.29 kg). Administration of exogenous testosterone to pregnant ewes over an interval of time approximating time of sexual differentiation in the fetus enhances postweaning growth rate, feed conversion efficiency and chemical composition of genetic females.
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PMID:Postweaning growth, feed efficiency and chemical composition of sheep as affected by prenatal and postnatal testosterone. 339 46

The synthetic non-steroidal antioestrogen nafoxidine (U-11, 100A) was given by mouth to 52 women with locally advanced or metastatic breast cancer, in 85% of whom the disease had become resistant to, or relapsed after, previous endocrine treatment. The objective response rate (complete or partial regression of disease) among 48 cases treated for at least four weeks was 37%. Tumours in soft tissue seemed to respond better than skeletal metastases. The patients in all but one of the 52 cases were postmenopausal. Those who had had an objective response to previous hormone treatment had a greater chance of deriving benefit from nafoxidine than those who had been resistant to hormone treatment.Side effects of nafoxidine were dryness of skin, increased loss of scalp hair, and heightened sensitivity to sunlight. None were serious, and they could be lessened by protection from solar radiation or a decrease in dosage. No obvious depression of thyroid or adrenal function or obvious water retention or masculinization was seen. Cataract was a possible complication.This clinical trial was preceded by laboratory studies in which a transplantable oestrogen-dependent tumour in the Syrian hamster was notably inhibited by the administration of nafoxidine. This experimental model may prove useful in screening potentially useful antioestrogenic agents against breast cancer before a human trial.
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PMID:Antioestrogens in treatment of breast cancer: value of nafoxidine in 52 advanced cases. 436 55

The last week of gestation is a critical period for the sexual differentiation of the brain in the rat. Exposure to prenatal stress during this period has been shown to demasculinize and/or feminize adult male sexual behavior. Many of the neurochemical and endocrine responses to hypoxia are similar to that observed under stressful conditions such as restraint stress. Therefore, we examined the postnatal consequences on reproductive and nonreproductive sexually dimorphic behaviors in male offspring of dams exposed to chronic hypoxia during the last week of gestation. In addition, we examined sensorimotor development in offspring of both sexes. Pregnant Sprague-Dawley dams were exposed to continuous hypoxia (10.5% O2 from gestational day 15 to 21). Offspring were weaned at 22 days of age and group housed. Behavioral tests were conducted with littermate representatives. In adulthood, male rats prenatally exposed to hypoxia had significantly delayed initiation latencies of masculine sexual behavior and decreased number of ejaculations, but did not display a significant increase in feminine sex behavior potentials. Developmentally, animals exposed to prenatal hypoxia did not differ significantly from controls with respect to day of eye or ear opening, or the in times of righting reflex, negative geotaxis or cliff avoidance. Wire hanging latencies in hypoxic exposed animals were significantly greater than controls around the time of eye opening, but did not differ at earlier or later ages. A significant effect of hypoxia was detected on stride length at 95 days of age, but other aspects of gait patterns were similar to controls. No group differences in gait patterns were observed at 17 or 45 days of age. In addition, no significant differences were observed in open field activity, circadian locomotor activity, saccharin preference, or Morris water maze test. This hypoxia regimen did not influence the occurrence of the prenatal or postnatal surge of plasma testosterone. Overall, these results provide some evidence that, in males, mild, chronic prenatal hypoxia may result in incomplete masculinization of adult reproductive behavior in the absence of overt changes in perinatal testosterone surges.
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PMID:Altered adult sexual behavior in the male rat following chronic prenatal hypoxia. 830 35

Ageing of the skin results from the synergistic effects of intrinsic ageing (due to age and genetic factors), photoageing (due to ultraviolet radiation) and, for women, hormonal ageing (due to oestrogen deficiency in postmenopausal women). Oestrogens receptors and metabolism or inactivation of oestradiol have been demonstrated in the skin, and the pilosebaceous unit is a target for sexual steroids. Could hormonal replacement therapy (HRT) be a treatment for the symptoms of skin ageing (dryness, roughness, burning and atrophy of the skin, itching, cold intolerance, wrinkles, hyperpilosity, alopecia)? In some experimental studies oestrogens increase the activity of fibroblasts and water, hyaluronic acid and collagen dermal contents. Some studies have demonstrated that oestrogen treatment increases skin thickness, mitotic activity of keratinocytes, and dermal collagen content in postmenopausal women. Thus HRT could theoretically treat skin ageing. It has been shown that HRT alleviates some symptoms of skin ageing (dryness of hair and skin) and that flushes disappear. We demonstrated that non-invasive measurements of physical parameters of the skin can reveal increase in skin thickness (+10 to +20 per cent) in women treated by HRT vs non treated, especially in the application area of oestrogen and in the non-sun-exposed areas. In our study HRT alleviated the hyposeborrhoea usually seen after menopause and could contribute to the amelioration of some complaints of post menopausal women such as roughness or dehydrated skin. Hormonal ageing is quantitatively less than actinic ageing, but its treatment is easier. Moreover HRT increases skin thickness, contributing to the prevention of atrophy (with fragile and fading skin) due to intrinsic ageing, and it limits the masculinization of facial hair and skin experienced by women as a sign of ageing. In conclusion HRT treats oestrogen deficiency and can be used to treat skin ageing.
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PMID:[Hormone replacement treatment and skin aging]. 876 22

Pleurodeles waltl is a newt with a ZZ male-ZW female sex determination mechanism, and a temperature-sensitive gonadal sex differentiation. Raising larvae at 32 degrees C from stage 42 to stage 54 (thermosensitive period) drives genetic females to differentiate into functional males. Estrogens are intimately linked with temperature action in this species, as well as in other vertebrates with temperature-dependent sex determination. We report here the masculinization of female ZW larvae and one WW larva by aromatase inhibitor treatment. Larvae were treated from stage 52 (before the onset of histological differentiation of the gonads) to stage 56 (metamorphosis), with the non-steroidal inhibitors fadrozole or miconazole. Miconazole proved to be very toxic, but not fadrozole. Fadrozole at a concentration of 300 micrograms/l in the rearing water resulted in complete sex reversal of 9 out of 30 ZW larvae and 1 out 9 WW larvae. Only one individual (ZW) was intersex, all the remainder being typical females. Gonadal aromatase activity was measured in several individuals at different developmental stages during treatment. The activity was low in all individuals at the beginning of the treatment, but varied strongly and was well correlated with gonadal structure at the end of the treatment. Despite these differences in individual responses to treatment inhibiting aromatase, results confirm the important role of estrogens in ovary differentiation in Pleurodeles waltl.
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PMID:Sex reversal by aromatase inhibitor treatment in the newt Pleurodeles waltl. 999 Jul 36

Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most contaminated areas is this exposure causally linked with the effects on reproductive organs that could have implications for fish populations. However, there is also a more widespread occurrence of endocrine disruption in fish in the U.K., where estrogenic effects have been demonstrated in freshwater systems, in estuaries, and in coastal areas. In mammals, the best evidence comes from the-field studies on Baltic gray and ringed seals, and from the Dutch semifield studies on harbor seals, where both reproduction and immune functions have been impaired by PCBs in the food chain. Reproduction effects resulted in population declines, whereas impaired immune function has likely contributed to the mass mortalities due to morbillivirus infections. Distorted sex organ development and function in alligators has been related to a major pesticide spill into a lake in Florida, U.S.A. The observed estrogenic/antiandrogenic effects in this reptile have been causally linked in experimental studies with alligator eggs to the DDT complex. Although most observed effects currently reported concern heavily polluted areas, endocrine disruption is a potential global problem. This is exemplified by the widespread occurrence of imposex in marine snails and the recent findings of high levels of persistent potential endocrine-disrupting chemicals in several marine mammalian species inhabiting oceanic waters.
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PMID:Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation. 1068 Jul 69

Female mosquitofish (Gambusia affinis holbrooki) downstream from Kraft paper mills in Florida display masculinization of the anal fin, an androgen-dependent trait. The current investigation was designed to determine if water contaminated with pulp-mill effluent (PME) from the Fenholloway River in Florida displayed androgenic activity in vitro and to relate this activity to the reproductive status of female mosquitofish taken from this river. We tested water samples for androgenic activity from a reference site upstream of a Kraft pulp and paper mill on the Fenholloway River, from 3 sites downstream from the mill, and from another reference site on the Econfina River, also in Florida, where there is no paper mill. We also examined anal fin ray morphology in mosquitofish from these rivers for evidence of masculinization. Eighty percent of the female mosquitofish from the Fenholloway River were partially masculinized while another 10% were completely masculinized, based upon the numbers of segments in the longest anal fin ray (18.0 +/- 0.4 vs. 28.1 +/- 0.9 [p < 0.001]) in the Econfina River vs. the Fenholloway River, respectively). In a COS whole cell-binding assay, all 3 PME samples displayed affinity for human androgen receptor (hAR) (p < 0.001). In addition, PME induced androgen-dependent gene expression in CV-1 cells (cotransfected with pCMV hAR and MMTV luciferase reporter), which was inhibited by about 50% by coadministration of hydroxyflutamide (1 microM), an AR antagonist. Water samples collected upstream of the Kraft mill or from the Econfina River did not bind hAR or induce luciferase expression. When CV-1 cells were transfected with human glucocorticoid receptor (hGR) rather than hAR, PME failed to significantly induce MMTV-luciferase expression. Further evidence of the androgenicity was observed using a COS cell AR nuclear-translocalization assay. PME bound hAR and induced translocalization of AR into the nucleus. In contrast, AR remained perinuclear when treated with water from the control sites (indicating the absence of an AR ligand). Interestingly, PME also displayed "testosterone-like" immunoreactivity in a testosterone radioimmunoassay, whereas water from the reference sites did not. In summary, water collected downstream of the Kraft mill on the Fenholloway River contains unidentified androgenic substances whose presence is associated with masculinization of female mosquitofish.
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PMID:Masculinization of female mosquitofish in Kraft mill effluent-contaminated Fenholloway River water is associated with androgen receptor agonist activity. 1145 38

The effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed in laboratory experiments. In this last of three publications, the responses of the fresh water snail Marisa cornuarietis and of two marine prosobranchs (Nucella lapillus, Nassarius (Hinia) reticulatus) to the antiandrogenic model compounds cyproterone acetate (CPA) and vinclozolin (VZ) are presented. The snails were exposed to nominal CPA concentrations of 1.25 mg/L alone and simultaneously to a potent synthetic estrogen (ethinylestradiol), androgen (methyltestosterone) or an indirectly acting xeno-androgen (tributyltin) in experiments with adult specimens and in a life cycle test for 12 months. Marisa and Nucella were furthermore exposed to nominal concentrations of 0.03-1.0 microgram VZ/L for up to 5 months. The antiandrogens induced a number of biological responses in all three species. The length of the penis and of accessory male sex organs (e.g., penis sheath, prostate) were significantly reduced. For Marisa, this effect occurred only in sexually immature specimens and was reversible as the males attained puberty. Typical androgen-mediated responses (imposex development, delayed spermatogenesis, tubulus necrosis of the testis with orchitis and Leydig cell hyperplasia) were partially or totally suppressed by a simultaneous administration of CPA. In the two marine species even adult, sexually mature males responded to antiandrogens with a reduction of the male sex organs and an advancement of the sexual repose phase. The results for CPA and VZ are compared with the effects of an exposure to xeno-estrogens (bisphenol A, octylphenol) and xeno-androgens (triphenyltin, tributyltin) in the same species. Each group of endocrine disruptors induces a characteristic set of toxicological effects in prosobranch snails which can be used as endpoints in an organismic invertebrate test for the identification of endocrine mimetic test compounds. Estrogens cause primarily an induction of superfemales resulting in an increased female mortality by the enhancement of spawning mass and egg production. The main effects of androgens are a virilization of females by imposex development and a marked decrease of the fecundity. Compared with estrogens and androgens, the antiandrogen responses seem to be less drastic and might have--in contrast to the two other disruptor classes--no biologically significant effects at the population level.
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PMID:Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part III: Cyproterone acetate and vinclozolin as antiandrogens. 1175 70


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