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Freeze-fracture observations on the intercellular junctions of Sertoli cells and of Leydig cells in the human testis.

Normal and feminized human testes were examined by means of freeze-fracture. In both cases, the junctional complexes between adjacent Sertoli cells show a unique characteristic feature. Many parallel linear occluding junctions are located circumferentially around the cell surface at the level of the nucleus. They are more than forty in number over one Sertoli cell surface. In the A face, the particles are not prominent on the ridge of the junctions. Instead, they are clearly seen in the center of the groove of the junctions on the B face. Gap junctions consisting of particle aggregation are not found between the Sertoli cells. The gap junctions between the Leydig cells are frequently observed in both normal and feminized testes. They are round or elliptic in contour and about several micrometers in diameter. The particles, about 8 nm in diameter, are closely packed to form a quasi-hexagonal pattern. The pits are found on the B face corresponding to the particle aggregation.

Adult↗

Extension of the Gender Identity Scale for Males.

Our earlier Femine Gender Identity Scale for males appear to measure a strong single factor which was reliable and displayed substantial discriminant validity. However, the number of items was small and there was substantial overlap between items with respect to their meaning. In an attempt to overcome these limitations, in the present study the scale was extended and validated. Each item of the new scale differentiated among the groups in an experimental sample and, subsequently, in a cross-validation sample. A secondary finding was the significantly higher femine gender identity scores of homosexual patients over homosexual nonpatients.

Adolescent↗

In ovo exposure to a triazine herbicide: effects of atrazine on circulating reproductive hormones and gonadal histology in young Japanese quail.

The triazine herbicide, atrazine, has come under scrutiny for its reported feminizing effects in amphibians. To date, there is little information concerning the effects of atrazine on reproduction in avian species. The current study examined the putative reproductive toxicity of atrazine after exposure in ovo. Atrazine at 504, 246, and 123 microg/kg was administered to Japanese quail eggs before incubation. The eggs were hatched and the birds raised to 14 days of age. Indices of hatchability, sex ratios, and growth were determined. Furthermore, circulating concentrations of reproductive hormones (estradiol, progesterone, and testosterone) and gonadal histology were examined. Atrazine at 504 microg/kg decreased 14-day hatchling weight by 13.1% versus controls. However, no detrimental effects on hatchability or sex ratios were observed. In female birds, atrazine at 504 microg/kg decreased ovarian weights and circulating concentrations of progesterone to 48.3% and 73.3%, respectively, versus control. However, concentrations of estradiol and testosterone did not differ from controls. In male quail, at all doses tested, atrazine had no effect on gonadal weights or circulating concentrations of estradiol, testosterone, or progesterone. Moreover, no incidences of left ovotestis formation were observed. In contrast, 10 ng/kg ethinylestradiol (a positive control) induced the formation of a left ovotestis in four of eight birds analyzed. The current results may suggest that exposure to atrazine in ovo at concentrations above ecologic relevance exerts effects on the reproductive system of young Japanese quail. However, no evidence is presented that atrazine induces feminization of the testis in male quail.

Animals↗

Cardinium symbionts induce haploid thelytoky in most clones of three closely related Brevipalpus species.

Bacterial symbionts that manipulate the reproduction of their host to increase their own transmission are widespread. Most of these bacteria are Wolbachia, but recently a new bacterium, named Cardinium, was discovered that is capable of the same manipulations. In the host species Brevipalpus phoenicis (Acari: Tenuipalpidae) this bacterium induces thelytoky by feminizing unfertilized haploid eggs. The related species B. obovatus and B. californicus are thelytokous too, suggesting that they reproduce in the same remarkable way as B. phoenicis. Here we investigated the mode of thelytokous reproduction in these three species. Isofemale lines were created of all three species and 19 lines were selected based on variation in mitochondrial COI sequences. All B. phoenicis and B. californicus lines (10 and 4 lines, respectively) produced males under laboratory conditions up to 6.7%. In contrast, males were absent from all B. obovatus lines (5 lines). Additional experiments with two B. phoenicis isofemale lines showed that males can be produced by very young females only, while older females produce daughters exclusively. For most lines it was shown that they are indeed feminized by a bacterium as treatment with antibiotics resulted in increased numbers of males up to 13.5%. Amplification and identification of specific gyrB sequences confirmed that those lines were infected with Cardinium. Three out of the five B. obovatus lines did not produce males after treatments with antibiotics, nor did they contain Cardinium or any other bacterium that might induce thelytoky. In these lines thelytoky is probably a genetic property of the mite itself. Despite the different causes of thelytoky, flow cytometry revealed that all 19 lines were haploid. Finally, the taxonomic inferences based on the mitochondrial COI sequences were incongruent with the classical taxonomy based on morphology, suggesting that a taxonomic revision of this group is necessary.

Animals↗

The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats.

Signs of feminization are seen in men with cirrhosis of alcoholic but also of nonalcoholic origin even in the absence of markedly increased plasma estrogen levels. Recently identified alterations of hepatic sex hormone receptor levels have provided a hypothetical mechanism for the pathogenesis of the feminization seen in cirrhotic men. The aim of the present study was to determine the effect of experimental portal-systemic shunting in adult male rats on hepatic sex hormone receptor levels, plasma sex hormones, and two markers for sex hormone action in the liver. The following alterations were found in male rats with surgically created portacaval shunts compared with sham-operated controls: the hepatic content of cytosolic estrogen receptors was reduced by 35% and the cytosolic androgen receptors content by 59%; plasma levels of estradiol increased 6.7-fold while those of testosterone were reduced by 71%; the estrogen-responsive ceruloplasmin levels were decreased by 31% and the androgen-responsive male-specific estrogen binder by 72%. Based on these data, it can be concluded that portal-systemic shunting reduces the hepatic cytoplasmic content of several sex hormone related proteins. These changes are paralleled by a decreased estrogen responsiveness of the liver, as evidenced by the plasma ceruloplasmin level.

Animals↗

Steroid hormones reverse sex in turtles.

Injection of estradiol benzoate into eggs of snapping turtles and painted turtles caused all embryos to develop as females. A similar but less consistent female-determining effect was associated with injection of testosterone proprionate. Both species of turtles have temperature-dependent sex determination in nature, whereby embryos incubated at cool temperatures (25 degrees) develop as males and embryos incubated at warm temperatures (31 degrees) develop as females. Exogenous estrogens have been shown to feminize embryos in a wide variety of reptiles, although feminization by estrogens as well as testosterone has been demonstrated previously in only one turtle (Pieau, 1974).

Animals↗

[Study of the synthesis of vitellogenin in intersexual males of Armadillidium vulgare Latreille (oniscoid isopod crustacean): comparison with males and with intact or ovariectomized females].

In some natural populations of Armadilidium vulgare, intersex animals are genetic males which are feminized by maternally transmitted symbiotic bacteria. In these intersex males (iM) the fat body synthesizes vitellogenin, although their gonads are testes with hypertrophied--but nonfunctional--androgenic glands. Vitellogenin is present in the hemolymph of males changed experimentally into iM 90 days after inoculation of the feminizing bacteria. During the molting cycle, vitellogenin synthesis in iM varies as in ovariectomized females or in vitellogenic females, with a peak at the stage D1." In A. vulgare, vitellogenin synthesis is a neutral character since it can be observed in a genetic male or in an ovariectomized female; however, it is inhibited by the androgenic hormone. In intersex males, vitellogenin synthesis is the result of their refractoriness to androgenic hormone.

Animals↗

Influence of dihydrotestosterone on sex determination in channel catfish and blue catfish: period of developmental sensitivity.

Treatment of channel catfish with 0.2, 20, or 200 mg/liter of dihydrotestosterone (DHT) in the water during the egg stage or during egg and sac-fry stages did not alter the expected 1:1 sex ratio of the progeny. Feeding DHT at 200 mg/kg of feed for the first 21 days after yolk sac absorption resulted in 80% females; this proportion was increased by combining feeding with treatment of 200 mg DHT/liter in the sac-fry stage (90%) or in the egg and sac-fry stage (97%). In contrast, treatment of blue catfish sac-fry with 200 mg DHT/liter, with or without the combination of feeding DHT at 200 mg/kg food, resulted in 100% female populations. Neither clomiphene citrate, an estrogen-receptor blocking agent, nor clofibrate, an inhibitor of hepatic synthesis of cholesterol, affected the sex ratio of channel catfish, and neither of these compounds altered the feminizing effect of 200 mg DHT/kg when fed in combination with DHT. The nonaromatizable androgen DHT is not as effective as many other androgens in producing paradoxical female populations of channel catfish. However, feminization of blue catfish by treatment of sac-fry indicates that this species is more susceptible to hormonal manipulation and that the period of sex determination may occur earlier in development than in channel catfish.

Animals↗

Hormonal control of sex differences in ultrasound production by hamsters.

Male and female hamsters differ in the stimulus control of the ultrasounds they produce during courtship and mating. In particular, untreated males show greater increases in ultrasound rate after exposure to stimulus females than after contact with other males. Conversely, estrous females are more responsive to stimulus males than females. This sex difference reflects both organizational and activational effects of gonadal hormones. Thus, responses to early castration or treatment with testosterone propionate (TP), estradiol benzoate (EB), or dihydrotestosterone propionate suggest that the development of male-like patterns of ultrasound production is facilitated by perinatal exposure to aromatizable androgen. However, even neonatally feminized subjects will show male-like calling if tested during adult treatment with TP. In contrast, the same subjects respond like naturally estrous females during adult treatment with EB plus progesterone (P). The contrasting responses of neonatally feminized subjects to later TP and EB + P treatments suggest that female hamsters retain a greater capacity for heterotypical patterns of ultrasound production than do males. This obviously differs from the common observation of greater "bipotentiality" for mating behavior in males. In turn, this suggests that the mechanisms controlling sexual bipotentiality are specific to their target behaviors, yielding distinct patterns of hormonal control for at least ultrasound production and lordosis.

Animals↗

Surgical treatment of intersex disorders.

Despite the progress made in understanding the factors regulating sexual differentiation, infants born with ambiguous genitalia face significant problems. The authors reviewed a group of 84 children with ambiguous genitalia managed surgically between 1986 and 1993. The most frequent condition was male pseudohermaphroditism (PM) (58%); 31% had female pseudohermaphroditism. Fifty-seven percent of patients were raised as males and 43% as females. In each group of patients, feminine and masculine reconstructive operations were performed. In only 31% of PM and 60% of PF cases was the diagnosis made within the first 2 months of life. In 41% of PF and 40% of PM patients, treatment was begun before the second year of life, which we consider an acceptable time. The timing and type of vaginoplasty were determined by the point of entry of the vagina into the urogenital sinus. Of the 29 patients reared as females, 22 required perineal vaginoplasty, had pull-through vaginoplasty, and 2 had colovaginoplasty. Since 1986, we have applied Mollard's clitoroplasty, which preserves the neurovascular bundle and is important for experiencing orgasm. Seventeen percent of patients with feminization procedures experienced complications. The optimal time for masculinization procedures is 2 years of age, after obligatory testosterone treatment. If there is utriculus prostaticus (UP) type II or III, it is removed before urethroplasty. This is not done for UP types 0 and 1. In PM cases, the number of feminization and masculinization operations was 2.1 and 4.05 per patient, respectively. It is easier to make a vagina than a phallus, not taking into consideration dimensions, aesthetics, or capability of erection of the phallus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The influence of gonadal steroids and the pituitary on the levels and composition of plasma phospholipids in the rat.

Gonadal steroids have been shown to influence plasma phospholipids. In the present study, the possible interaction between gonadal steroids and the pituitary in the regulation of plasma phospholipids was studied in rats. The total phospholipid concentration (higher in females) and the fatty acid composition of plasma lecithin was different in male compared to female rats. Gonadectomy resulted in a "feminization" of plasma phospholipids (total concentration and fatty acids in lecithin) in male rats but had no effect in females. Testosterone treatment of gonadectomized males or intact females resulted in a "masculinization" of plasma phospholipids, whereas estrogen treatment of intact males resulted in a "feminization." Hypophysectomy resulted in a marked decrease in plasma phospholipid concentration and the fatty acid composition of lecithin showed a "masculine" pattern in both males and females. Neither testosterone nor estrogen treatment had any effects on plasma phospholipids in hypophysectomized male and female rats, respectively. It is concluded that gonadal steroids and the hypothalamic-pituitary axis interact in the regulation of the synthetic and perhaps also degradative pathways controlling plasma phospholipids.

Animals↗

Facilitory effects of male urine on feminine behavior in the male rat: androgen-dependency.

Feminine behavior in the male rat can be enhanced by exposing ORCH animals primed with estradiol benzoate and progesterone to the odor of urine collected from intact male adult congeners [20]. The present study provides evidence that this pheromonal effect is androgen dependent. A higher proportion of ORCH feminized rats displayed lordosis behavior following exposure to the odor of urine for either intact male rats or from ORCH rats supplemented with testosterone propionate than did ORCH feminized rats exposed to the odor of urine originating from non injected ORCH males.

Animals↗

Olfactory cues from the female can affect feminine behavior in the male rat.

The aim of this work was to study the influence of the hormonal milieu on the facilitory effects of olfactory stimuli originating from female urine on lordosis behavior in orchidectomized (ORCH) feminized rats. Urine from ovariectomized (OVX) rats was shown to increase the proportion of ORCH rats displaying lordosis behavior, an effect which was enhanced if the OVX rats had been given progesterone. Treatment of OVX rats with estradiol benzoate did not affect the pheromonal activity of their urine. Dexamethasone treatment of OVX rats completely suppressed the facilitory effects of their urine on the feminine behavior in males. A higher proportion of feminized rats displayed lordosis following exposure to urine collected from pseudopregnant rats than did their unexposed counterparts. Dexamethasone treatment of pseudopregnant rats did not abolish this effect. These results suggest that the adrenal cortex is capable, in the absence of the ovaries, of manufacturing some pheromonal substance which stimulates feminine behavior in the male rat. The nature of this substance remains unknown. Furthermore progesterone itself is involved in the emission of olfactory signals which control feminine behavior in the male rat.

Androstenedione↗

Embryonic sex steroids affect mating behavior and plasma LH in adult chickens.

Chicken embryos of both sexes were treated with either antiestrogen (tamoxifen = T), antiandrogen (flutamide = F), aromatization inhibitor (ATD = A), estradiol (E), or oil (control = C). Before puberty, some males of each group were castrated. At puberty, birds were tested under the following regimes: castrated males injected daily with testosterone propionate (CAS + TP) or estradiol benzoate (CAS + EB), intact males (M-INT), intact females (F-INT), and females injected daily with TP (F-TP). In the M-INT and CAS + TP males, E treatment suppressed masculine mating behavior. The embryonic treatments with T, F, and A demasculinized only the frequency of copulations. None of the antihormone treatments caused any masculinization of the sexual activity in the F-TP birds. Untreated males had higher plasma LH than females. The embryonic treatment with E reduced (feminized) the LH levels in CAS + EB birds. This effect was less pronounced in M-INT birds. The results suggest that in chickens, estradiol plays a role in the masculinization of copulatory behavior potential in the developing male embryo. High embryonic estradiol reduces the potential for displaying male sexual behavior at puberty. Feminization of LH secretion requires a high level of estradiol in both embryonic and adult life.

Androstatrienes↗

Gonadal steroids influence neurophysin II distribution in the forebrain of normal and mutant mice.

The distribution of arginine vasopressin-associated neurophysin (neurophysin II) immunoreactivity was investigated in normal and mutant house mice during development and after various gonadal steroid manipulations. During postnatal development of normal mice dense networks of neurophysin II immunoreactivity in the lateral septal nucleus and lateral habenular nucleus appeared earlier in male than in female mice, with an adult pattern of immunoreactivity being attained by 8 weeks and 12 weeks of age, respectively. The neurophysin II immunoreactivity in the male was denser than that in female mice. After gonadectomy of adult normal mice there was a gradual loss of neurophysin II immunoreactivity in the lateral septum and lateral habenula over a period of 15 weeks. In hypogonadal mice, a mutant in which gonadal development is arrested postnatally due to a deficiency in hypothalamic gonadotrophin releasing hormone, no immunoreactive neurophysin II could be detected in the lateral septum or lateral habenula. A pattern of neurophysin II immunoreactivity similar to that in normal control mice was observed in hypogonadal mice which had been implanted for 4 weeks with silicone elastomer capsules containing testosterone or oestradiol-17 beta, but not 5 alpha-dihydrotestosterone or progesterone. Stimulation of gonadal development and endogenous steroid production in hypogonadal mice by third ventricular grafts of preoptic area tissue from normal neonatal animals also produced a normal pattern of neurophysin II immunoreactivity in the lateral septum and lateral habenula. In the androgen-insensitive testicular feminized mouse immunoreactive neurophysin II was undetectable in the lateral septum and lateral habenula. Treatment of testicular feminized mice with oestradiol-17 beta, but not progesterone, produced a normal pattern of neurophysin II immunoreactivity. The main immunohistological findings were confirmed by radioimmunoassay of tissue extracts which showed that the concentration of arginine vasopressin in lateral septum was far greater in normal males than females and was undetectable in hypogonadal mice; no oxytocin could be detected in the septum of normal or hypogonadal mice. These results show that the expression of neurophysin II immunoreactivity in the lateral septum and lateral habenula of the mouse brain is dependent on the presence of aromatizeable androgens or oestrogens.

Aging↗

Hormonal contributions to sexually dimorphic behavioral development in humans.

Nineteen studies on the behavioral effects of prenatal exposure to hormones administered for the treatment of at-risk human pregnancy are reviewed. Because the role of prenatal exposure to hormones in the development of human behavioral sex differences is potentially confounded by society's differential treatment of the sexes, comparisons between exposed and unexposed subjects were evaluated and summarized separately for male and female subjects. Therefore, this review focuses on data for individuals whose prenatal hormone environments were atypical relative to what is normal for their own sex. Overall, it appears that prenatal exposure to androgen-based synthetic progestin exerted a masculinizing and/or defeminizing influence on human behavioral development, whereas prenatal exposure to natural progesterone and progesterone-based synthetic progestin had a feminizing and/or demasculinizing influence, particularly among female subjects. The data on prenatal exposure to synthetic estrogen derive primarily from subjects exposed to diethylstibestrol (DES). DES-exposed male subjects appeared to be feminized and/or demasculinized, and there is some evidence that exposed female subjects were masculinized. These findings are discussed in the context of prenatal hormonal contributions to sexually dimorphic behavioral development both within and between the sexes. Recommendations for the conduct of future research in developmental behavioral endocrinology are presented.

Behavior↗

Sexual orientation in male rats prenatally exposed to ethanol.

Previous studies have shown that prenatal ethanol exposure causes feminization of the male offspring, as evidenced by display of female sexual response (lordosis), when mounted by a stud male. In the present study we examined whether or not the feminization induced by prenatal ethanol exposure also affected a different aspect of sexually motivated behavior, namely, the approach towards a receptive female normally displayed by male rats. The testing apparatus consisted of an open-field arena with two small boxes in which were placed the stimulus animals, in one box a male rat, in the other a receptive female. The partition between the stimulus and the experimental animals consisted of a metal net allowing both animals to see and smell each other without actual physical contact. The tendency to approach the receptive female or the male was assessed by the proportion of the observation period the experimental male spent near the receptive female or the male rat, respectively. The experiment was performed on the adult male offspring of mothers consuming a liquid diet containing 5% ethanol, giving rise to a daily ethanol intake of about 14 g/kg. One group of control mothers was given a liquid diet without alcohol but isocaloric with the alcohol-containing diet. Another control group had free access to water and lab chow. The results showed that male offspring of both control groups devoted 29% of the observation period near the receptive female as compared to 13% near the male. The ethanol-exposed males on the other hand devoted as much time, 20%, to the male as to the receptive female.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats.

Prenatal maternal stress in rats and mice can demasculinize and feminize the sexual behavior of adult male offspring. Causal mechanisms are unknown, but one attractive hypothesis is that stress activation of maternal adrenal glucocorticoid secretion is the responsible agent. To test this hypothesis, pregnant rats were exposed to a variety of substances which enhance glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams and a positive stress control group (restraint under bright lights three times daily). All treatments reduced maternal weight gain, DEX most potently. No treatment altered litter size, stillbirths, or sex ratio, but DEX reduced weight at birth, an effect still seen at postnatal day 85. DEX, CORT, and stress reduced male adrenal weight at birth, while DEX and CORT altered sexual differentiation as measured by anogenital distance. Stress impaired adult male sexual performance but not the lordosis quotient following exposure of animals to stud males. DEX affected both measures. No other treatment had any significant effect on sexual behavior. No treatment altered plasma LH levels, either basal or in response to an estrogen challenge in adult gonadectomized males. In adulthood there was no treatment effect on stress reactivity, measured behaviorally or by plasma glucocorticoids. Correlational analysis revealed that weight gain during pregnancy was the single best predictor of subsequent sexual performance. It is concluded that prenatal dexamethasone exposure demasculinizes and feminizes male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗