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PubMed1991

Hormonal control of behaviour: steroid action in the brain.

There have recently been significant advances in our understanding of the cellular action of steroids on brain mechanisms of behaviour. Brain cells contain steroid metabolizing enzymes whose activity is modified by environmental stimuli. Steroids have rapid effects on neurotransmitter receptors via cell membranes and modify the distribution of neuropeptide receptors in areas controlling behaviour. It has been known for some time that oestrogens have an effect on brain structure that can be related to behaviour in the sexually dimorphic avian song system. Recent work suggests that oestrogen may have a similar effect on the developing sexually dimorphic nuclei of the mammalian brain.

Animals↗
PubMed2002

Poor uterine development in Turner syndrome with oral oestrogen therapy.

OBJECTIVE: To evaluate uterine development in Turner syndrome (TS) patients in relation to treatment with oral ethinyl oestradiol (E2 ) for pubertal induction. DESIGN AND PATIENTS: Pelvic ultrasound data for 96 TS patients scanned since 1989 were analysed. Patients were classified into three groups: (1) untreated (n = 48); (2) complete spontaneous puberty (n = 10); and (3) treated with ethinyl oestradiol (n = 38). Uterine development was described in the three groups and compared with the normal data. MEASUREMENTS: Uterine length, fundal-cervical ratio (FCR) and shape were recorded, and presence or absence of ovaries noted. In the treated group, cross-sectional and longitudinal data were combined to compare uterine development with Tanner breast stage. RESULTS: In untreated girls up to age 10 years there was a variable distribution of uterine length and FCR about the mean. Thereafter, the uterus failed to grow and mature normally. Girls with complete spontaneous puberty had morphologically normal ovaries and uteri, but of 7 girls who attained menarche, 3 subsequently developed secondary oligomenorrhoea or amenorrhoea. In the treated group, in general, breast development and uterine length progressed with increasing E2 dose. However, only 50% of girls with complete secondary sexual development had a mature heart-shaped uterine configuration. CONCLUSIONS: Our current E2 treatment regimen for TS girls gives rise to satisfactory pubertal induction and maintenance, but failed to induce a fully mature uterus in half the cohort. In view of the high risk of miscarriage in TS in both spontaneous and assisted pregnancies, the effect of more physiological methods of E2 replacement on uterine development should be investigated.

Adolescent↗
PubMed1999

Molecular characterization of tol, a mediator of mating-type-associated vegetative incompatibility in Neurospora crassa.

The mating-type locus in the haploid filamentous fungus, Neurospora crassa, controls mating and sexual development. The fusion of reproductive structures of opposite mating type, A and a, is required to initiate sexual reproduction. However, the fusion of hyphae of opposite mating type during vegetative growth results in growth inhibition and cell death, a process that is mediated by the tol locus. Mutations in tol are recessive and suppress mating-type-associated heterokaryon incompatibility. In this study, we describe the cloning and characterization of tol. The tol gene encodes a putative 1011-amino-acid polypeptide with a coiled-coil domain and a leucine-rich repeat. Both regions are required for tol activity. Repeat-induced point mutations in tol result in mutants that are wild type during vegetative growth and sexual reproduction, but that allow opposite mating-type individuals to form a vigorous heterokaryon. Transcript analyses show that tol mRNA is present during vegetative growth but absent during a cross. These data suggest that tol transcription is repressed to allow the coexistence of opposite mating-type nuclei during the sexual reproductive phase. tol is expressed in a mat A, mat a, A/a partial diploid and in a mating-type deletion strain, indicating that MAT A-1 and MAT a-1 are not absolutely required for transcription or repression of tol. These data suggest that TOL may rather interact with MAT A-1 and/or MAT a-1 (or downstream products) to form a death-triggering complex.

Amino Acid Sequence↗
PubMed1979

Transient partial hGH deficiency in prepubertal children with delay of growth.

UNLABELLED: The hGH response to an ornithin or an insulin test was measured in 105 children from 11-18 yr old with delay of growth more than 2 SD. Besides 74 subjects with normal values and 7 with complete lack of response, 24 subjects exhibited a partial rise of GH. Most of the latter had decreasing growth rate and no sign of puberty. Out of 15 assessed for GH function after onset of puberty, 14 showed a normal response accompanying a markedly increased growth velocity. Four other subjects with partial response who were receiving sexual hormones for 48 hr before the second test showed a normal response also. An exogenous hGH treatment administered in two of these patients resulted in a marked and sustained growth increase far before entering puberty. SPECULATION: The findings that plasma GH responses to stimulation tests is reduced in some children with decreasing growth rate before puberty and return to normal after onset of sexual development, would suggest a transient and functional defect in growth hormone secretion and the physiologic role of sexual hormones on GH release mechanism at that period of life.

Adolescent↗
PubMed1994

Hormonal therapy of male hypogonadism.

The goals of hormonal treatment of male hypogonadism depend upon the stage of sexual development in which gonadal failure occurs. Androgen replacement therapy is used to induce and maintain normal secondary sexual characteristics, sexual function, and behavior in prepubertal boys and men with either primary or secondary hypogonadism. Parenteral testosterone esters, testosterone enanthate or cypionate, are the most effective, safe, practical, and inexpensive androgen preparations available for this purpose. They are the treatment of choice for androgen replacement therapy. A recently approved scrotal transdermal testosterone system provides an alternative to testosterone esters in selected patients. In boys or men with secondary hypogonadism, gonadotropin or GnRH therapy may be used instead of testosterone therapy to stimulate endogenous testosterone production. Because of their greater expense and complexity, however, these modalities are usually reserved for men with gonadotropin deficiency who desire fertility and in whom spermatogenesis must be initiated and maintained. Gonadotropin therapy is begun with hCG alone. In men with partial or previously treated gonadotropin deficiency, or in men with postpubertal hypogonadotropic hypogonadism, hCG treatment alone may be sufficient to stimulate spermatogenesis and fertility. In most men with prepubertal hypogonadotropic hypogonadism, however, combined treatment with hCG plus hMG is needed to initiate sperm production and fertility. Pulsatile GnRH therapy may be used to stimulate testosterone production and spermatogenesis in men with secondary hypogonadism who have hypothalamic defects, such as idiopathic hypogonadotropic hypogonadism or Kallmann's syndrome.

Androgens↗
PubMed1997

Sexual expression and dementia. Views of caregivers: A pilot study.

OBJECTIVE: To measure the attitudes of health professionals in nursing homes towards sexuality and sexual expression in cognitively impaired and cognitively intact residents. DESIGN: Postal survey. PARTICIPANTS: The staff (administrators, clinicians, social workers and others) of 300 randomly selected nursing homes located in three states. Of these, 114 representatives responded. MAIN OUTCOME MEASURE: A measure of attitudes towards resident sexuality developed during a prior study. RESULTS: Results suggest that respondents held a generally positive orientation towards residents' sexual expression which was expressed with respect to cognitively impaired residents as well as to those who were cognitively intact. Possibly because of the small sample size and resulting low statistical power, statistical analyses failed to demonstrate any significant differences among the groups of residents: administrators, clinicians, social workers, and undifferentiated 'others'. However, while non-significant, there was a consistent tendency for administrators to be relatively more conservative than were the other groups. Almost all respondents agreed that additional staff training should focus specifically on dealing with resident sexual expression. CONCLUSIONS: Overall, the sample reported generally positive attitudes towards resident sexuality and sexual expression.

Aged↗
PubMed2007

A pilot intervention to enhance psychosexual development in adolescents and young adults with cancer.

BACKGROUND: Evidence suggests that cancer diagnosed during adolescence and young adulthood may present considerable challenges to what would otherwise be a relatively smooth developmental trajectory, particularly in areas related to reproductive health. We created and pilot tested a two-session, individually-delivered, counseling intervention to enhance psychosexual development in this unique population. PROCEDURES: A total of 21 patients, aged 15 to 25 years and treated for cancer within the past 5 years, completed the counseling intervention. Patients were adaptively randomized to begin the intervention immediately, or to be placed on a 3-month waitlist, after which time, they were reassessed and began the intervention. The content of the intervention included education, dialog, and support regarding cancer and such issues as sexual development and function, body image, fertility, prevention of sexually transmitted disease and unwanted pregnancy, and romantic relationships (e.g., dating, sexual communication). A 1-month follow-up booster call followed the intervention. Questionnaires were completed at baseline, post-waitlist (for half the sample), post-treatment, and at 3-month follow-up. RESULTS: Participation in the intervention increased cancer-specific knowledge regarding sexual issues; improved body image; lessened anxiety about sexual and romantic relationships; and decreased overall level of psychological distress. Gains were maintained through the 3-month follow-up. CONCLUSIONS: Addressing issues of reproductive health in the adolescent/young adult with cancer can and should be offered as a part of comprehensive pediatric cancer care.

Adolescent↗
PubMed1976

Developmental patterns of plasma and pituitary TSH and prolactin and hypothalamic TRH in the female rat.

In developing female rats, pituitary content and concentration of TSH and prolactin measured twice daily (1000 and 1600 h) were low during the first two weeks of life and increased markedly between day 15 and 30. AM-PM variations in pituitary levels of both hormones were apparent, particularly during this latter phase of development. Plasma TSH levels increased between days 5 and 12, showing peak values at this age. After day 15, levels declined gradually to reach a nadir shortly before puberty. At puberty, plasma TSH remained low, showing only minor fluctuations. No consistent AM-PM differences in plasma TSH were observed at any age studied. Plasma prolactin was low between day 5 and 15, increasing thereafter. Starting at day 10, AM-PM fluctuations in plasma levels were detected, titers being higher in the afternoon than in the mornings. It has already been reported (Endocrinology 98: 630, 1976) that during puberty this pattern becomes more evident, peak values being reached in the afternoon of the first proestrus. Hypothalamic TRH content increased between day 5 and 15, reaching a maximum at this age and declining thereafter to adult values. No qualitative changes in pituitary TSH during development were observed, as determined by exclusion chromatography. The existence of divergent patterns of plasma TSH and prolactin during female sexual maturation and the fact that hypothalamic TRH titers than with prolactin levels suggest that the mechanism(s) that stimulates pituitary release of these two hormones during sexual development is different.

Animals↗
PubMedDate not supplied

[Sex differentiation and its anomalies].

Sex determination and differentiation is a sequential process that involves genetic, gonadal, phenotypic and psychological sex. Sex determination is primarily testis determination. The primary event is differentiation of the gonad; all subsequent sexual differentiation is hormonally controlled. The Authors present a classification of abnormal sexual development and consider the errors of primary sex differentiation (anomalies of sex chromosomes and of gonadogenesis) and the errors of sexual differentiation (inadequate masculinization of genetic male and virilization of genetic female). At the end the clinical approach to disorders of sexual differentiation is briefly considered.

Androgen-Insensitivity Syndrome↗
PubMed1975

Effects of modification of the social environment on young monkey development.

Experiments and observations of the effects of modifications of the social environment on the young primate's relationship with its mother and its social-sexual development have begun to delineate the large number of variables that determine and affect the attachment relationship and that are contingent upon it. Attachment can occur to a number of mother substitutes, including a dog. Early experience has special importance but young monkeys are surprisingly responsive and adaptable to substitute maternal stimuli. The quality of developing social behavior is dependent on both the quantity and quality of an attachment. We have yet to learn what are the critical component stimuli which make up an adequate early social environment for young monkeys and apes.

Animals↗
PubMed1975

Stimulation of repoduction in captivity of the wild rabbit, Oryctolagus cuniculus.

Female wild rabbits which failed to breed under laboratory conditions were treated with gonadotrophins and artificially inseminated with epididymal spermatozoa. The fertilized eggs so obtained were transferred to synchronous domestic rabbits. Altogether, 185 eggs were transferred to thirty-six recipients. Thirty-three of the recipients maintained pregnancy to term and nearly half of the transferred eggs developed into normal young. Birthweights ranged from 45 to 59 g. Postnatal survival was excellent. Females born in captivity remained sexually immature in spite of attaining normal adult body weights. Sexual development was apparently normal in the males, although most remained shy breeders. Incidental observations on ovarian response, egg size and rate of development are presented.

Animals↗
PubMed1991

[Prolactin, ovarian and adrenal steroid hormone in relation to the vaginal opening in immature female rats].

The serum prolactin levels in human girls are thought to be increased gradually throughout puberty, but some authors have reported that prolactin decreases transitorily before menarche. Prolactin has not been shown to play a significant role on the initiation of human pubertal development. However, in immature female rats, it is thought that prolactin is one of the most important hormones during sexual maturation. In experiment I, the serum concentrations of prolactin, estradiol (E2) and dehydroepiandrosterone-sulfate (DHA-S) in immature female rats were measured. Prolactin increases gradually before vaginal opening and tends to decrease after vaginal opening, while E2 increases throughout sexual maturation. No significant changes were noticed in DHA-S levels. In experiment II, sulpiride, which raises serum prolactin level, was injected daily in to 4 groups of immature female rats starting from 14, 21, 28, and 35 days of age till the day before vaginal opening. Physiological saline solution was injected daily in to age-matched controls. On the day of vaginal opening, serum levels of prolactin, E2 and DHA-S were studied, weights of bodies and internal genital organs were measured, and corpora lutea of the ovaries were inspected. Vaginal opening was accelerated in the group of rats injected with sulpiride 5mg every morning from 14 days of age (p less than 0.05). The weights of their bodies and internal organs were less than those of the control rats (p less than 0.05). Percent of ovaries which contained corpora lutea were lower than the controls. Although their serum levels of prolactin tended to be suppressed, three hormone levels were not different from those of control rats on the day of vaginal opening. However, when mean prolactin levels were depicted on the day of vaginal opening in both groups, a peak was noticed at 37 days of life, indicating that the secretion pattern of this hormone has been programmed according to the day of life. There was a close relation between prolactin and DHA-S levels (p less than 0.05). No significant relation between prolactin and E2 levels was noticed. The possible role of prolactin and DHA-S on the regulation of sexual development is suggested. To our knowledge, this is the first demonstration of a significant relation between prolactin and DHA-S in immature female rats.

Age Factors↗
PubMed1983

Effects of steroid hormones on pituitary immunoreactive gonadotropin in European freshwater eel, Anguilla anguilla L.

The low pituitary immunoreactive gonadotropin (IR GTH) contents of immature female or male freshwater eels were strongly increased after intraperitoneal injections of estradiol. Using female eels, the effect was shown to be dose dependent. In neither sex was modification of pituitary IR GTH observed after progesterone treatment; a very small increase (significant in females but not in males) was produced by cortisol. An important sexual difference occurred with testosterone, which strongly stimulated pituitary IR GTH level in male but not in female eels. The possibility of a low central aromatase activity responsible for the lack of effect of testosterone in the female eel is discussed. Circulating IR GTH levels were very low in steroid-treated eels, as in controls, indicating a weak GTH release. Thus, as in juvenile, immature fish from other species, a sexual steroid stimulated eel pituitary GTH content; the peculiarity of the apparent "blockade" of eel sexual development appears not related to a lack of sensitivity of gonadotropin synthesis to the positive feedback of a sexual steroid.

Anguilla↗
PubMedDate not supplied

The androgen receptor (AR) in syndromes of androgen insensitivity and in prostate cancer.

The actions of androgens, principally testosterone and 5alpha-dihydrotestosterone, are mediated by a specific receptor protein, the androgen receptor (AR), which is encoded by a single-copy gene located on the human X-chromosome. This receptor protein is a prototypical member of the nuclear receptor family and modulates a range of processes during embryogenesis and in the adult. During embryogenesis, normal AR function is critical to the development of the male phenotype and defects of the AR cause a range of phenotypic abnormalities of male sexual development. Complete loss of AR function has been traced to a number of distinct types of genetic events, including abnormalities of mRNA splicing, the introduction of premature termination codons, and amino acid substitution mutations. An interesting subset of mutations is that in which the AR is completely undetectable using sensitive immunoassays. In all instances, these functional abnormalities are associated with a phenotype of complete androgen insensitivity (complete testicular feminization). By contrast, partial defects of AR function are almost invariably caused by amino acid substitutions within the DNA- and hormone-binding domains of the receptor protein. Such partial defects of receptor function may be caused by changes in either receptor function or receptor abundance. The alterations of AR function and expression that have been characterized in clinical prostatic cancers and in prostate cancer cell lines differ in several important respects. A number of studies have documented the emergence of considerable heterogeneity of AR expression at early stages in the development of prostate cancer. Despite these early changes of AR expression, a substantial body of information suggests that the AR is expressed in advanced forms of prostate cancer, in some cases as the result of amplification events. While infrequent in localized tumors, mutations of the AR have been identified in a number of advanced prostatic cancers and in some instances appear to alter the ligand specificity of the AR. Finally, it appears that other signaling pathways can act to influence AR function.

Androgens↗
PubMed2002

Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2.

Unlike many features of metazoan development, sex determination is not widely conserved among phyla. However, the recent demonstration that one gene family controls sexual development in Drosophila, C. elegans, and vertebrates suggests that sex determination mechanisms may have evolved from a common pathway that has diverged radically since the Cambrian. Sex determination gene sequences often evolve quickly, but it is not known how this relates to higher-order pathways or what selective or neutral forces are driving it. In such a rapidly evolving developmental pathway, the fate of functionally linked genes is of particular interest. To investigate a pair of such genes, we cloned orthologs of the key C. elegans male-promoting gene fem-3 from two sister species, C. briggsae and C. remanei. We employed RNA interference to show that in all three species, the male-promoting function of fem-3 and its epistatic relationship with its female-promoting upstream repressor, tra-2, are conserved. Consistent with this, the FEM-3 protein interacts with TRA-2 in each species, but in a strictly species-specific manner. Because FEM-3 is the most divergent protein yet described in Caenorhabditis and the FEM-3 binding domain of TRA-2 is itself hypervariable, a key protein-protein interaction is rapidly evolving in concert. Extrapolation of this result to larger phylogenetic scales helps explain the dissimilarity of the sex determination systems across phyla.

Amino Acid Sequence↗
PubMed1983

The adolescent patient.

The physician must establish a confidential and trusting relationship with the adolescent patient. All states allow treatment of adolescents over 18 without parental consent and some allow treatment for special problems such as venereal disease or drug abuse before 18. The depressed adolescent often presents with behavioral problems, school failure, or medical symptoms. The medical history should include a description of the pregnancy and delivery, immunizations and childhood diseases, family history of coronary disease, sexual activity, school performance, and drug use. The physical examination should include an evaluation of growth and sexual development, blood pressure determination, a breast examination in older teenagers, and a pelvic examination if the patient is sexually active or if a gynecologic problem is suspected. All adolescent patients need a urine analysis and hematocrit test. Sexually active patients need a serologic test for syphilis, gonorrhea culture, and Papanicolaou smear. Determination of cholesterol and triglyceride are needed when there is a history of a myocardial infarction in a first-degree relative younger than age 50 years.

Adolescent↗
PubMed2000

Glutamatergic regulation of gonadotropin releasing hormone mRNA levels during development in the mouse.

The aims of these studies were to investigate the time course of the increase in gonadotropin releasing hormone (GnRH) mRNA levels during sexual development in the mouse, and to test the hypothesis that the neurotransmitter glutamate regulates the GnRH secretory system via actions at the level of GnRH gene expression. GnRH mRNA abundance was estimated by measuring silver grains generated by in situ hybridization of an 35S-labelled oligonucleotide probe. There was a significant increase in GnRH mRNA abundance between the day of birth (P0) and postnatal day 2 (P2) in male mice, but no further increases at later ages when overt pubertal changes are manifest. GnRH mRNA levels also increased significantly between P0 and P2 in female mice. Treatment with the glutamate agonist NMDA caused a significant increase in GnRH mRNA levels in neonatal (P0) mice and adult male mice within 30 min of treatment, which is consistent with previous studies in the rat implicating glutamate in the regulation of GnRH mRNA stability. Treatment with the glutamate antagonist CGP40116 caused an equally rapid decrease in GnRH mRNA levels in adult mice and in mice on P5 after the neonatal increase in GnRH gene expression, but was without effect in mice on P0, prior to the developmental increase. These observations that the effect on GnRH mRNA levels of blocking endogenous glutamatergic signalling depends upon the developmental stage suggest that endogenous glutamate maintains GnRH mRNA levels in adult mouse, and is a potential regulator of the developmental increase seen in the neonatal period.

2-Amino-5-phosphonovalerate↗
PubMed2002

Androgen receptor mutations and androgen insensitivity.

The androgen receptor (AR) is a high affinity receptor protein encoded on the human X-chromosome that mediates the actions of androgens during development and in the adult. Defects in this receptor protein result in a wide range of abnormalities of male sexual development. Studies in a number of different laboratories have identified mutations of the AR gene in subjects with androgen resistance syndromes. Defects that interrupt the AR open-reading frame have been traced to a number of distinct types of genetic alterations, have been identified in widely separated segments of the AR gene, and are invariably associated with the phenotype of complete androgen insensitivity. By contrast, mutations that cause single amino acid substitutions within the AR are localized to the DNA- or ligand-binding domains of the receptor protein and have been associated with the full range of androgen resistant phenotypes. The diversity of mutations that have been identified has prompted a consideration of the relationship between AR mutation and phenotype. Analyses of AR abundance and function suggest that the phenotypic abnormalities that result from mutation of the AR reflect the extent to which AR activity is impaired in target tissues. Such decreases in AR function may be the result of the diminished receptor function, decreases in receptor concentration, or a combination of these two effects.

Androgen-Insensitivity Syndrome↗