The effects of androgens on fetal sexual development: androgen-induced female pseudohermaphrodism.
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Androgens↗
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Abnormal sexual development in children.
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Disorders of Sex Development↗
Abnormal sexual development in infancy.
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Disorders of Sex Development↗
Secondary sexual development of 'Cape Coloured' girls following kwashiorkor.
This report describes the secondary sexual development of 45 'Cape Coloured' female ex-kwashiorkor patients and 43 female controls. All patients were originally seen between five months and four years four months of age, treated and then followed up for 15 years after discharge. Age at menarche was available on 42 ex-patients and 33 controls, and age at peak height velocity (PHV) was available for 30 ex-patients and 15 controls. Maximum likelihood estimates of the mean age at entry to each pubertal stage were made, age at menarche was obtained directly from the subject records and age at PHV was obtained by fitting a non-linear growth function to the data for each subject. All subjects passed through the sequence of pubertal events in the normal order, i.e., no reversals were observed. Ex-patients were generally delayed in relation to controls but there were no significant differences for ages at entry to any of the pubertal stages. The subjects were combined for comparison to equivalent data on British girls. The South African girls were significantly delayed in the development of pubic hair and menarche but showed no significant differences for age at entry or duration of breast development and PHV. It is suggested that lack of delay in breast development may have selective advantages to females living in situations of chronic malnutrition.
Female↗
Müllerian-inhibiting substance function during mammalian sexual development.
To investigate the role of Müllerian-inhibiting substance (MIS) in mammalian sexual development, we generated MIS-deficient mice. Although MIS-deficient males had testes that were fully descended and produced functional sperm, they also developed female reproductive organs, which interfered with sperm transfer into females, rendering most of these males infertile. Their testes had Leydig cell hyperplasia and, in one instance, neoplasia. The actions of the two primary hormones of male sexual differentiation were genetically eliminated using the testicular feminization (Tfm) mutation in combination with the MIS mutant allele. XY Tfm/MIS double mutants developed as females, with a uterus, coiled oviducts, and no male reproductive organs except undescended dysfunctional testes. These results suggest that eliminating the presumptive female reproductive tract in male fetuses facilitates fertility and that in testes MIS is a negative regulator of Leydig cell proliferation. Eliminating the presumptive male reproductive tract is necessary for proper oviductal morphogenesis during female mouse development.
Androgen-Insensitivity Syndrome↗
Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development.
The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that differential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), alpha-tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor kappaB (NFkappaB) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NFkappaB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.
Animals↗
[Sexual development in adolescents after surgical treatment for cryptorchidism].
OBJECTIVE: To investigate the sexual development in adolescents after surgical treatment for undescended testes. METHODS: One hundred and eighty-four adolescents undergoing surgery for cryptorchidism before the age of 10 years, 22 cases received no surgical management for unilateral undescended testes, and 25 normal controls were studied. The pubic stage, the natural length and girth of the penis, the volume of the testis, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were examined to find out the effect of age, the location of the testis and operative procedures on prognosis. RESULTS: The pubic stage, the length and girth of the penis, the volume of the testis and T decreased, but FSH and LH increased significantly in 18 adolescents who had undergone bilateral orchiopexy. The volume of the unilaterally undescended testis was significantly smaller than that of the normally descended contralateral gonad in 152 adolescents who had undergone unilateral orchiopexy. FSH was significantly higher in the adolescents surgically treated for unilateral cryptorchidism. Those treated by unilateral orchiectomy presented significantly higher levels of FSH than those by unilateral orchiopexy. The pubic stage, the length and girth of the penis, the volume of the testis and T were significantly higher, but FSH lower in the adolescents treated before the age of 5 years than at the age of 5 or older. The decrease in testicular volume was significantly greater in adolescents with intra-abdominal testes. Significant negative correlation was found between FSH and testicular volume. CONCLUSION: Leydig cell function seems relatively resistant to the hostile environment of the cryptorchidism. Early diagnosis and management of the undescended testis are needed to preserve fertility.
Adolescent↗
Regulation of sexual development in the basal termite Cryptotermes secundus: mutilation, pheromonal manipulation or honest signal?
Social insect colonies are not the harmonious entities they were once considered. Considerable conflicts exist between colony members, as has been shown for Hymenoptera. For termites, similar studies are lacking, but aggressive manipulations have been claimed to regulate sexual development, and even to account for the evolution of workers. This study on a basal termite, Cryptotermes secundus (Kalotermitidae), suggests that the importance of aggressive manipulations in termites has been overemphasized. Wing-bud mutilations, a means proposed to regulate the development of dispersing sexuals (alates), seem to be artifacts of handling conditions that cause disturbance. Aggressive behaviors never occurred unless colonies were disturbed. Theoretical considerations further showed that the potential for intense conflict among termite nestmates is low compared to hymenopteran societies. Strong conflicts are only expected to occur over the replacement of natal reproductives that died, while less intense conflicts should exist over the development into alates when food in the colony becomes limiting. Accordingly, intracolonial aggressive interactions over replacement are common, whereas nestmates seem to manipulate alate development via proctodeal feeding when food resources decline. However, the latter is rather an honest signal than a manipulation because only the most competent prospective dispersers can impede the development of nestmates.
Aggression↗
Effect of cyclic sound cues on sexual development in nonphotostimulated Japanese quail.
The influence of cyclic ambient sound stimuli on sexual development was studied in nonphotostimulated [6 hr light:18 hr dark (16L:18D)] Japanese quail (Coturnix coturnix japonica). The incidence of accelerated gonadal development was reduced when ambient daily sound stimuli were attenuated by the presence of a white noise mask in the animal quarters. In a second experiment nonphotostimulated (9L:15D) male quail showed a phase-dependent testicular response to a daily 3-hr radio broadcast presented at different portions of the day. The radio sound stimulus induced a higher incidence of accelerated gonadal development when presented 6 hr prior to the photophase than when presented either 3 hr prior to the photophase or when presented coincidently with the photophase onset. In a third experiment locomotion was monitored in nonphotostimulated quail (9L:15D) with a 3-hr radio sound stimulus presented 6 hr prior to photophase onset. The onset of a daily locomotor activity pattern was associated with radio sound in some individuals, but sound-induced locomotion was not consistently associated with sound-induced accelerated gonadal development.
Acoustic Stimulation↗
Detection of endocrine disrupters: evaluation of a Fish Sexual Development Test (FSDT).
Managed by the Organisation for Economic Co-operation and Development (OECD), a comprehensive work is carried out in numerous laboratories to develop test guidelines for the detection of endocrine disrupting chemicals in humans, and various animal species. Development of tests to detect chemicals with endocrine disrupting properties in fish is a part of that work. A Fish Sexual Development Test (FSDT) (an extension of the existing OECD TG 210, fish early life stage toxicity test), proposed as an international test guideline for the detection of endocrine disrupting chemicals, was evaluated by water exposure of juvenile zebrafish to the three natural estrogens: estrone, 17beta-estradiol, and estriol and the synthetic androgen trenbolone (trenbolone acetate). As endpoints, vitellogenin induction and histological changes including changes in sex ratios were investigated. The sex ratio was significantly altered towards females from 49 ng/l estrone, 54 ng/l 17beta-estradiol and 22 microg/l estriol, respectively. An all male population was observed from exposure to 9.7 ng/l trenbolone and above. Significant vitellogenin induction in whole body homogenate was measured after exposure to 14 ng/l estrone, 54 ng/l 17beta-estradiol and 0.6 mug/l estriol, respectively. Significant vitellogenin reduction was measured after exposure to 193 ng/l trenbolone or higher. The present results provide strong evidence that the FSDT is a sensitive test toward estrogenic and especially androgenic exposure and the validation of the FSDT as an OECD test guideline should continue.
Animals↗
Sexual development of patients with isochromosomes for the long arm of the X chromosome.
The sexual development of 14 girls with non-mosaic monocentric 46,X,iXq karyotype was studied. Seven out of eight girls were found to have immature secondary sexual characteristics and amenorrhoea, a finding greatly contrasting with that in Triplo-X girls. The relative ineffectiveness of the isochromosome Xq in maintaining fertility may be due to the absence of one short arm, which probably also carries a gonadal determinant. Alternatively, the presence of two inactivation sites on one isochromosome may render the gonadal determinants inactive at an important stage in gonadal development.
Adolescent↗
The effects of immunization against luteinizing hormone-releasing hormone on performance, sexual development, and levels of boar taint-related compounds in intact male pigs.
The effect of a newly developed anti-LH-RH vaccine on the performance, sexual development, and incidence of boar taint-related compounds was investigated in young intact male pigs. At 29 kg BW, 40 crossbred intact males and 20 castrates were allocated to three groups. Castrates and half of the intact males were untreated. The remaining intact males were immunized against LH-RH at 29 kg and again at 89 kg BW. All pigs were slaughtered at 105 kg BW. Compared with control intact males, feed efficiency in castrates was decreased by 10%, muscle content was reduced by 5%, and carcass fat content was increased by 26%. Growth performance and carcass traits did not differ significantly between immunized and control intact males. Genital tract weight, measured at slaughter, was decreased (P < or = .002) by immunization. Plasma testosterone concentrations were not significantly affected at 89 kg BW, whereas they were sevenfold lower (P < .001) in immunized than in control intact males at 105 kg BW. Fat androsterone levels, measured at slaughter, were substantially reduced (P < .001) from .66 +/- .07 microgram/g in control to .21 +/- .01 microgram/g in immunized intact males. Rates of testicular steroid biosynthesis, measured in vitro, were decreased by immunocastration. Fat skatole levels were very low and did not differ significantly between the three groups. The present results demonstrate that anti-LHRH immunization was effective in reducing the level of androstenone, a boar taint-related compound, although having a limited effect on the performance of the animals.
Adipose Tissue↗
Puberty without gonadotropins. A unique mechanism of sexual development.
Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.
Child↗
Effect of nutrition during calfhood and peripubertal period on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls.
The objective of the present study was to characterize the effects of nutrition on circulating concentrations of metabolic hormones, gonadotropins, and testosterone during sexual development in bulls. Nutrition regulated the hypothalamus-pituitary-testes axis through effects on the GnRH pulse generator in the hypothalamus and through direct effects on the testes. Pituitary function (gonadotropin secretion after GnRH challenge) was not affected by nutrition. However, nutrition affected LH pulse frequency and basal LH concentration during the early gonadotropin rise (10-26 weeks of age). There were close temporal associations between changes in insulin-like growth factor-I (IGF-I) concentrations and changes in LH pulse frequency, suggesting a role for IGF-I in regulating the early gonadotropin rise in bulls. The peripubertal increase in testosterone concentration was delayed in bulls with lesser serum IGF-I concentrations (low nutrition), suggesting a role for IGF-I in regulating Leydig cell function. Serum IGF-I concentrations accounted for 72 and 67% of the variation in scrotal circumference and paired-testes volume, respectively (at any given age), indicating that IGF-I may regulate testicular growth. Bulls with a more sustained elevated LH pulse frequency during the early gonadotropin rise (high nutrition) had greater testicular mass at 70 weeks of age relative to the control group (medium nutrition), despite no differences in metabolic hormone concentrations after 26 weeks of age. Therefore, gonadotropin-independent mechanism regulating testicular growth might be dependent on previous gonadotropin milieu.
Animals↗
Growth and sexual development before and after sex steroid therapy in patients with thalassemia major.
Growth, sexual development, and hypothalamic-pituitary-gonadal function were evaluated in 23 patients with thalassemia major (14 female and nine male) aged 13 to 29 years. Five women (group 1) with hemoglobin levels of less than 7 g/dL, which were maintained by transfusions during childhood, did not spontaneously enter puberty. They had evidence of severe hypothalamic-pituitary dysfunction. Maintaining hemoglobin levels of about 8 g/dL resulted in spontaneous onset of puberty in seven of nine female patients (group 2), but had no such ameliorative effect on the nine male patients. In the latter, peak luteinizing hormone (LH) responses to gonadotropin releasing hormone correlated with bone age. Treatment with testosterone produced inconsistent partial inhibition of LH and follicle-stimulating hormone (FSH) responses to stimulation. After discontinuation of testosterone treatment, a rebound of basal testosterone, LH, and FSH levels was observed, but this was not sustained. These findings are compatible either with dysfunction of hypothalamic maturation or with partial pituitary dysfunction. Four of the group 1 females and six of the males treated with appropriate sex hormones showed satisfactory pubertal progression. Acceleration in linear growth was observed in four of the male patients whose epiphyses were still open. Treatment was well tolerated in all patients.
Adolescent↗
Health, growth and sexual development of teenagers exposed in utero to medroxyprogesterone acetate.
General health, growth and sexual development were evaluated in 74 teenage boys and 98 girls who had been exposed to medroxyprogesterone acetate (MPA) in utero, and 385 boys and 448 girls not exposed. In this 17-year prospective study, the ascertainment of the end points was 'double blind' in that neither the interviewer nor the subject was aware of our interest in MPA. On average, girls exposed to MPA reported reaching the menarche 4 months earlier than the comparison group. This difference disappeared, however, in a multiple regression analysis taking into account social class, the mother's age at menarche and height of the girl's mother and father. Boys exposed to MPA reported their growth spurt to have occurred an average of 6 months earlier and voices to have broken 5 months earlier than unexposed boys. Again, the differences between them and the comparison group disappeared after controlling for confounding variables. There were no significant differences between the MPA-exposed and comparison groups in a wide variety of indices of health reported by the teenagers' mothers. These findings are consistent with the hypothesis that intrauterine exposure to MPA, in the doses used for pregnancy maintenance or for contraception, poses no threat to the long-term health and development of the progeny.
Adolescent↗
HCG stimulation test in children with abnormal sexual development.
Plasma testosterone was estimated by radioimmunoassay in 60 children with disorders of sexual development before and after stimulation with human chorionic gonadotrophin (HCG). In 21 children the testosterone levels after 3 and 5 daily injections of 1000 units HCG were compared and good correlation was found between the paired results (r =0-93), suggesting that the 5-day HCG test has no advantage over the 3-day test. In 7 boys with apparently normal genital development the increments in plasma testosterone ranged from 2-0 to 8-5 nmol/1 after 3 injections of HCG. 10 boys with anorchia showed little response to HCG stimulation, but in patients with other disorders, such as micropenis (10), cryptorchidism (8), hermaphroditism (3), male pseudohermaphroditism (13), hypospadias (3), and sex chromosome anomalies (6), there was considerable variation in the plasma testosterone level after HCG. In 2 boys with suspected anorchia the results suggested that testes were present and this was confirmed at operation.
Adolescent↗
Sexual development and free-running period in quail kept in constant darkness.
In Japanese quail (Coturnix coturnix japonica) sexual development may occur in total darkness (DD). Linked to sexual maturation, variations of the rhythm of feeding activity were observed: in DD, the amount of activity increased and the period of the free-running rhythm lengthened. During the first weeks in DD all the quails presented a free-running period less than 24 hr (22.3 +/- 0.5 hr; N = 50). At the end of the experiment, the more a bird was mature, the greater the lengthening of its period. In DD, testosterone implants in castrated male quails can mimic these modifications but we failed to find any correlation between the number of implants (i.e., the level of testosterone) and the extent of the lengthening.
Activity Cycles↗