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Effects of prenatal antiandrogen treatment on masculinization and defeminization of guinea pigs.

Gonadectomized (gdx) guinea pigs which had received the antiandrogen flutamide prenatally were tested for female-typical and male-typical sexual behavior in adulthood. In tests for lordosis behavior, gdx males and females were injected with estradiol benzoate and progesterone. Prenatally flutamide-treated females showed a longer mean lordosis response than control females. This was true whether they were given either a high or a low dose of EB. No male ever showed a lordosis response. In tests for male-typical sexual behavior, gdx adult males were treated with testosterone propionate and tested with stimulus females. The prenatally flutamide-treated males showed significantly decreased levels of ejaculation, a lower intromission rate and a decreased percentage of mounts which included pelvic thrusts, when compared to control males. Mount rate and rate of pericopulatory behavior did not differ between the flutamide and control males. The fact that prenatal administration of flutamide increased female-typical behavior in adult females suggests that the female guinea pig is normally partially defeminized by androgens in utero. The male guinea pig appears to be resilient to attempts to block defeminization with prenatal antiandrogens. However, some aspects of masculinization can be blocked.

Androgen Antagonists↗

Extrahypothalamic serotonergic modification after masculinization induced by neonatal gonadal hormones.

Exposure to gonadal steroids during the critical period exerts an organizational effect on the CNS. This hormonal effect could be mediated, at least in part, by neurotransmitters. Traditionally, the main place involved in the aminergic sexual differentiation has been the hypothalamus. The aim of this work was to examine the possible long-term effect of cerebral administration of testosterone or estradiol on sexual behavior and hypothalamic/extrahypothalamic monoaminergic systems in the adult rat. For this purpose, female Wistar rats were intraventricularly injected during the first 24 h of life with testosterone (T) or estradiol benzoate (EB) (200 micrograms/kg) (male and female control groups were vehicle treated) and sexual behavior and monoaminergic mediobasal hypothalamic, striatal, and limbic metabolism in adult rats were studied. Receptive behavior was not affected, whereas a masculinizing effect (% mounts) was observed in the animals treated with both gonadal hormones. Only testosterone-treated females showed a male-like serotonergic ratio in corpus striatum and limbic system. A possible extrahypothalamic serotonergic role could be suggested in the mechanisms of sexual differentiation.

Animals↗

Muscarinic and nicotinic influences on masculine sexual behavior in rats: effects of oxotremorine, scopolamine, and nicotine.

In this study, the role of cholinergic systems in the regulation of male sexual behavior was analyzed by different approaches. Both muscarinic agonists and antagonists, as well as a nicotine agonist, were administered to sexually experienced male rats. In Experiment 1, oxotremorine (OXO), a muscarinic agonist, decreased the intromission frequency and ejaculatory latency in a dose-dependent way. Moreover, an increase in ejaculatory frequency was observed. In Experiment 2, the muscarinic antagonist scopolamine (SCO) produced a dose-related impairment of sexual behavior, decreasing the percentage of sexually active males. The smaller doses of SCO delayed the initiation of sexual behavior and decreased ejaculatory frequency. In an attempt to analyze the effect of muscarinic supersensitivity on sexual behavior, in Experiment 3 a long-term blockade of muscarinic receptors (SCO for 17 days) was followed by OXO administration. Animals displayed a significant increase of mount frequency, which results in the decrease of both the hit rate and ejaculatory frequency. In Experiment 4, six doses of nicotine were acutely administered. Only the higher doses (0.4, 0.8, and 1.6 mg/kg) induced a decrease in intromission frequency, although no significant differences were found in any other parameter. These results strongly suggest that cholinergic participation in masculine sexual behavior regulation is mediated mainly through muscarinic system.

Animals↗

Prepubertal testosterone treatment of neonatally gonadectomized male rats: defeminization and masculinization of behavioral and endocrine function in adulthood.

Testosterone (T) administered well after the neonatal "critical" period to females at a dose approximating male levels permanently defeminizes reproductive function (see companion publication). To obtain comparable data for the male, neonatally gonadectomized (NeoGx) males received T filled or empty Silastic capsules during days 15-30 of age and were studied in adulthood. Compared to controls, the T treatment resulted in reduced lordosis and proceptive behaviors, increased mounting and intromission behaviors without differences in penile reflexes or size, and reduced plasma FSH and LH surges. Twenty of twenty-three sham-NeoGx males, but only one NeoGx male, showed ejaculatory behavior despite equivalence in penile reflexes and size after detaching a frenulum when present on the penis. These results show that T can still act on neural substrates well beyond the neonatal period to defeminize and masculinize endocrine and behavioral function in the male rat. A comparison with effects in females indicates a sex difference, the male appearing to be more sensitive to these actions of T.

Animals↗

Masculinization of growth hormone (GH) secretory pattern by dihydrotestosterone is associated with augmentation of hypothalamic somatostatin and GH-releasing hormone mRNA levels in ovariectomized adult rats.

The role of androgen in the sexual dimorphism in hypothalamic growth hormone (GH)-releasing hormone (GHRH) and somatostatin (SS) gene expression was examined in rats. In the first study, the SS and GHRH mRNA levels were measured in both male and female rats at 4, 6, 8, and 10 weeks of age. A significant sex-related difference in the SS and GHRH mRNA levels was observed after 8 weeks of age, when sexual maturation is fully attained. Male rats had higher SS and GHRH mRNA levels than the female rats. In the second study, adult ovariectomized rats received daily injection of dihydrotestosterone (DHT), nonaromatizable testosterone, at a dose of 2 mg/rat for 21 days. The DHT treatment masculinized the GH secretory pattern, which was indistinguishable from that of intact male rats, and simultaneously augmented the SS and GHRH mRNA levels. The DHT treatment of ovariectomized rats after hypophysectomy significantly raised the level of SS mRNA, but not that of GHRH mRNA compared to the control animals. These findings suggest that the activation of the SS gene expression through androgen receptor plays an important role in the maintenance of sexual dimorphism in GH secretion in rats.

Animals↗

Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46,XX congenital virilizing adrenal hyperplasia and 46,XY androgen-insensitivity syndrome compared.

Among 30 young women with a history of the treated adrenogenital syndrome (CVAH), 11 (37%) rated themselves as bisexual or homosexual. Among a control group consisting of 15 women with the 46,XY androgen-insensitivity syndrome (AIS) plus 12 with the Rokitansky syndrome (MRKS), the corresponding figure was 2 (7%), both bisexual. Chi-square was significant beyond the 0.01 level. In Kinsey's 1953 sample 15% of women experienced homoerotic arousal imagery by age 20, and 10% had had homoerotic partner contact. The most likely hypothesis to explain the CVAH findings is that of a prenatal and/or neonatal masculinizing effect on sexual dimorphism of the brain in interaction with other developmental variables.

Adrenal Hyperplasia, Congenital↗

Masculinity and undocumented labor migration: injured latino day laborers in San Francisco.

Drawing on data collected through clinical practice and ethnographic fieldwork, this study examines the experience of injury, illness and disability among undocumented Latino day laborers in San Francisco. We demonstrate how constructions of masculine identity organize the experience of embodied social suffering among workers who are rendered vulnerable by the structural conditions of undocumented immigrant status. Theoretical concepts from critical medical anthropology and gender studies extend the scholarly analysis of structural violence beyond the primarily economic to uncover how it is embodied at the intimate level as a gendered experience of personal and familial crisis, involving love, respect, betrayal and patriarchal failure. A clinical ethnographic focus on socially structured patriarchal suffering elucidates the causal relationship between macro-forces and individual action with a fuller appreciation of the impact of culture and everyday lived experience.

Adult↗

Effects of an androgenic growth promoter 17beta-trenbolone on masculinization of Mosquitofish (Gambusia affinis affinis).

Endocrine disrupting chemicals can affect normal hormone dependent processes through numerous mechanisms, including ligand mimicky. 17beta-Trenbolone (TB), a pharmaceutical, androgenic, anabolic steroid, is a potent agonist of androgen receptors, and has been extensively used as a growth promoter for beef cattle in the US. The effects of TB on adult and newborn mosquitofish (Gambusia affinis affinis) were examined. Two forms of mosquitofish androgen receptor (AR), ARalpha and ARbeta, were cloned. The mRNA expression levels of ARalpha and ARbeta were transiently increased in the anal fin of adult females at day 3 following exposure to TB (1-10 microg/L) or methyltestosterone (MT) (0.1-10 microg/L), a pharmaceutical androgen used as a positive control. Gonopodium differentiation from the adult female anal fin was induced after 28 days of exposure to TB (1-10 microg/L) or MT (0.1-10 microg/L). Gonopodium differentiation also was induced in all mosquitofish fry exposed for 28 days to 0.3, 1 or 10 microg/L TB. Furthermore, spermatozoa were observed histologically in the testes of male fry exposed for 28 days to 1 or 10 microg/L TB; spermatozoa are normally observed only in the testes of mature males. Surprisingly, all female fry exposed for 28 days to 1 or 10 microg/L TB displayed the formation of an ovotestis, as spermatozoa were found in the ovary. Thus, TB, like MT, induced masculinization of the anal fin accompanied by a transient up-regulation of ARalpha and ARbeta in adult females. TB also induced differentiation of the anal fin into a gonopodium in fry of both sexes, stimulated precocious spermatogenesis in the testes of males and the formation of ovotestes in females.

Amino Acid Sequence↗

Masculinized otoacoustic emissions in female spotted hyenas (Crocuta crocuta).

In humans and rhesus monkeys, click-evoked otoacoustic emissions (CEOAEs) are stronger in females than in males, and there is considerable circumstantial evidence that this sex difference is attributable to the greater exposure to androgens prenatally in males. Because female spotted hyenas are highly androgenized beginning early in prenatal development, we expected an absence of sexual dimorphism in the CEOAEs of this species. The CEOAEs obtained from 9 male and 7 female spotted hyenas confirmed that expectation. The implication is that the marked androgenization to which female spotted hyenas are exposed masculinizes the cochlear mechanism responsible for CEOAEs. The CEOAEs measured in 3 male and 3 female hyenas that had been treated with anti-androgenic agents during prenatal development were stronger than the CEOAEs of the untreated animals, in accord with the implied inverse relationship between prenatal androgen exposure and the strength of the cochlear mechanisms producing CEOAEs. The CEOAEs of three ovariectomized females and two castrated males were essentially the same as those for the untreated females and males, suggesting that there is little or no activational effect of hormones on CEOAE strength in spotted hyenas. Distortion product OAEs (DPOAEs) also were measured. Those sex differences also were generally small (as they are in humans), and the effects of the anti-androgen agents were inconsistent. Thus, prenatal androgen exposure apparently does affect OAEs, but the effects appear to be greater for the reflection-based cochlear mechanism that underlies CEOAEs than for the nonlinear cochlear mechanism underlying DPOAEs.

Androgen Antagonists↗

Autogenic masculinization.

We present a case in which self-treatment of lichen sclerosus with large doses of topical testosterone resulted in marked masculinization and may have caused secondary amenorrhea. These changes have not previously been reported as side effects of topical testosterone use.

Adult↗

Masculinization of a female fetus by Krukenberg tumor during pregnancy.

A case of fetal masculinization resulting from a Krukenberg tumor in a pregnant woman is reported in a newborn infant with a sexual ambiguity of the external genitals, of the feminine pseudohermaphrodite type. She also had an incarceration of both ovaries and tubes in a right inguinoscrotal hernia that was surgically corrected.

Disorders of Sex Development↗

A new 1-stage procedure for clitorovaginoplasty in severely masculinized female pseudohermaphrodites.

A new 1-stage procedure for clitorovaginoplasty in severely masculinized female pseudohermaphrodites is presented. The technique consists of clitoral reduction with preservation of the neurovascular supply to the glans and vaginal formation by joining the inverted penile skin and the divided distal "urethra" (urogenital sinus) to form a cylinder that is then inserted into the perineum and anastomosed to the true vagina. For high and small vaginas Monfort's transtrigonal approach is suggested. This operation, 4 of which have been performed to date, can be done at any age, and it offers excellent cosmetic and functional results.

Child, Preschool↗

Prenatal social stress masculinizes the females' behaviour in guinea pigs.

This study investigated the influence of the social environment during pregnancy and lactation on the female offsprings' behaviour and body weight. The subjects studied were daughters whose mothers had lived: a) in a stable social environment (SSE) during pregnancy and lactation; b) in an unstable social environment (USE) during pregnancy and lactation; c) in a SSE during pregnancy but in an USE during lactation; d) in an USE during pregnancy but in a SSE during lactation. The SSE was made by keeping the group composition (one male, five females) constant; in the USE situation every third day two females from different groups were exchanged. After weaning (n = 4 x 3 = 12), groups of daughters, consisting of four females each, were established, originating from the different categories of mothers. From their 41st through their 80th day of age the spontaneous behaviour of the daughters was recorded in their home cages. When the mothers had lived in an USE during pregnancy, the daughters displayed significantly higher amounts of male-typical courtship, play, and social orientation behaviour compared to daughters whose mothers had lived in a SSE during pregnancy. The stability and instability, respectively, of the social environment during lactation, however, had no significant influence on the daughters' prospective behaviour. The four categories of daughters did not differ in their body weights either at birth or at 80 days of age. Thus, the instability of the social environment during pregnancy obviously represented a mild stressor that nevertheless caused a distinct masculinization of the daughters' behaviour.

Animals↗

Fetal alcohol exposure blocks full masculinization of the dorsolateral nucleus in rat spinal cord.

Male rats prenatally exposed to a combination of stress and ethanol show severely impaired ejaculatory patterns. This study examined two sexually dimorphic nuclei in the lumbar spinal cord implicated in the control of male copulatory reflexes in rats whose mothers were exposed to alcohol, to stress, or to both treatments during pregnancy. Alcohol exposure led to a marked decrease (22%) in the number of motor neurons in the dorsolateral nucleus (DLN) of the adult male offspring, but no significant change in cell count was detectable in the sexually dimorphic nucleus of the bulbocavernosus (SNB). The combination of alcohol and stress did not enhance the effect on the DLN above that produced by alcohol alone. Somal sizes in the DLN and SNB were not altered by any of the treatment conditions. Alcohol exposure probably leads to incomplete masculinization of the DLN in male rats by decreasing testicular steroidogenesis during the fetal stage(s) when sexual differentiation is ongoing in that CNS structure.

Animals↗

Uptake and depletion of plasma 17alpha-methyltestosterone during induction of masculinization in muskellunge, Esox masquinongy: effect on plasma steroids and sex reversal.

Oral administration of 17alpha-methyltestosterone (MT) was used to induce masculinization of sexually undifferentiated muskellunge, Esox masquinongy. Three groups of muskellunge (mean weight, 2.5 +/- 0.6 g) were submitted to MT treatment (15 mg of MT/kg) for 60 days. An additional one group was used as a control (hormone-free diet). Food was distributed over a 10-h period by using automatic belt feeders. Blood was sampled in both control and treated fish at different intervals during and after feeding: before (0 h), at 3 h, 6 h, and cessation of feeding (10 h), and after a fast of 22 h (32 h). MT had no significant effect on growth and survival in muskellunge 6 months after the treatment. Concentrations of plasma MT increased during the feeding period and reached their maximum levels 6 or 10 h after starting feeding. This rapid increase of MT indicated a rapid absorption of this steroid. Plasma MT levels then declined and reached a radir by 22 h after cessation of feeding, suggesting that MT is rapidly metabolized and excreted. The profiles of plasma testosterone during the MT treatment did not differ significantly between control and MT-treated groups. During and after the MT treatment, the concentration of plasma testosterone did not differ significantly between control and MT-treated groups. Moreover, no sexual dimorphism of testosterone levels was observed. Six months after treatment, the sex ratio in MT-treated groups (33% males, 62% females, and 5% intersex) was opposite to control (70% and 30%, respectively) and differed significantly. This suggests that at 15 mg of MT/kg over 60 days, a paradoxical feminization took place.

Animals↗

Masculine sexual behavior features in the Flinders sensitive and resistant line rats.

The Flinders sensitive (FSL) and resistant (FRL) lines of rats have been selectively bred for their differences in cholinergic sensitivity. The FSL rats display hypersensitive responses to agonists of muscarinic receptors. In addition, the FSL rats display behavioral alterations that support the notion that this strain could be useful as an animal model of depression. These abnormalities include increase in rapid eye movement sleep, decrease of saccharin consumption after stress, and reduced exploratory behavior in a novel open field. On the other hand, sexual behavior is a pleasure-seeking behavior that should be altered in a mood disorder characterized by anhedonia. In the present study, spontaneous masculine sexual behavior features were analyzed, both during 30-min tests as well as during a satiety test. Results showed that, compared to outbred Sprague-Dawley (SD) rats, both the FSL and the FRL rats displayed some behavioral impairment, like a marked decrease of the ejaculatory frequency. During the satiety tests, both the FSL and the FRL rats became exhausted sooner than their SD controls. In addition to considering the present results in terms of alterations in specific neurotransmitter systems, endogamy is proposed as a possible source of the behavioral alterations.

Animals↗

[Diversity and meaning of masculine phallic palaeolithic images in Western Europe].

The archaeological record necessary to understand the sexual behaviour of our ancestors from Upper Palaeolithic (38.000-8.500 B.C.) is limited. Traditionally the ethnographic information about sexuality and the relations between sexes derived from comparitions with current primitive human groups have been considered very important, although they have been evaluated more from a social and anthropological rather than biological perspective. Ice age art art, both rock and portable, is a reflection of the behaviour of palaeolithic human groups. The purpose of this text focuses on understanding the types of representations and sexual attitudes during the Upper Palaeolithic, as reflected from masculine images of phallic character. Practices of foreskin retraction, some phalli possibly circumcised, copulative acts, expressions of masturbation, instruments that have been likely been used for masturbation and other sexual scenes, some of which are difficult to interpretate, show that the sexual behaviour of the human groups of the Upper Palaeolithic were similar to ours, both from a biological and physiological viewpoint.

Animals↗

[Hepatitis B and ratio of masculinity].

Among families of blood donors from Languedoc, found to be chronic carriers of HBs antigens, the masculinity ratio of the siblings (number of boys compared to number of girls) calculated on 303 individuals is significantly higher (1,32) than that of the general population (1,05). This rise is still increased when considering only the families where the viral infection is present in the mother (1,73), whereas it is very low when in the father (1,09).

Blood Donors↗