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PubMed1987

ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen.

Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic-pituitary axis, which leads to an increase in LH and testosterone secretion. A new non-steroidal antiandrogen ICI 176,334 [2RS)-4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200 micrograms/kg) for 7 days to immature castrated rats, ICI 176,334 (10 mg/kg) significantly (P less than 0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25 mg/kg for 14 days to adult rats caused a dose-related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen-responsive benign and malignant diseases.

Androgen Antagonists↗
PubMed1994

[Urogenital malformation complex including the Mullerian system].

Symptomatic cystic epididymis in a 21-year-old man led to the detection of several genital malformations, including a partially obstructing pelvic cyst, prostatic and bilateral testicular atrophy and penoscrotal hypospadias. These malformations are probably due to a deficiency of either testosterone or müllerian inhibiting hormone (MIH). Development of the male genitalia is influenced by testosterone secreted in the Leydig cells during weeks 8-16 of gestation, while regression of the müllerian ducts is induced by MIH secreted in the Sertoli cells from weeks 9-12 of gestation.

Abnormalities, Multiple↗
PubMed1997

Plasma testosterone level and the male genital system after chloroquine therapy.

Chloroquine phosphate and its analogue hydroxychloroquine are used on long term basis as anti-inflammatory drugs in the treatment of a multitude of chronic diseases. In the present work the dose of the drug was calculated and given to albino rats in the usual low therapeutic regimen used in man. This work has shown that chloroquine depresses testosterone secretion in a progressive manner which increased the longer the duration of treatment, sperm count was also decreased, the percent of abnormal forms increased and the weight of the testes and accessory sex organ (epididymis, vas deference, seminal vesicle and prostate) was also reduced, these abnormalities did not return to the normal control figures, even after one month of discontinuation of the drug. This work emphasizes the need for testosterone administration concomitantly with chloroquine treatment to maintain the integrity of the sexual organs of the patients. At the same time this work emphasizes the need of further study of the reversibility of the pathological lesions in the male genital tract after more prolonged administration of the drug than the three months period adopted in the present work.

Animals↗
PubMedDate not supplied

[Endocrinology of cryptorchidism].

The testicular descent into the scrotum depends on a series of complex endocrine and mechanical interactions. The first stage or transabdominal that occurs during the first 3 months of gestation is probably produced by the differential growth of the fetus and is believed to be mediated by the Müllerian inhibiting hormone. The second stage or transinguinal migration that occurs during the 8th month of gestation is a complex event depending on the interaction between the hypothalamic-pituitary-testicular hormonal axis and mechanical factors as gubernaculum, intra-abdominal pressure, epididymis. This stage is believed to be androgen dependent. Although hormonal involvement in testicular descent appears clear-cut, there is nevertheless some discrepancy in the literature as to whether cryptorchid children show abnormalities in their hypothalamic-pituitary-testicular axis. Certainly cryptorchidism is a syndrome with various causes. Few cases show primary anatomical abnormalities or are associated to complex congenital anomalies or to clear hormonal defects. Most cases do not recognize an evident cause and an endocrinological abnormality has been suggested. A deficiency in LH and testosterone secretion has been reported in the cryptorchid child.

Adolescent↗
PubMed1999

Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys.

OBJECTIVE: Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubertal development. In order to explore this question, we measured serum PSA levels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes. DESIGN: Sera from 77 normal boys in Tanner stages I to V (T-I to T-V) were analysed for PSA levels by a sensitive time-resolved fluoro-immunometric assay (sensitivity: 0.012 microgram/l). In addition, sex hormone binding globulin (SHBG), insulin like growth factor I (IGF-I), IGF binding protein 3(IGFBP-3) and testosterone were measured. RESULTS: PSA was detectable in 0% of Stage T-I (n = 16), 33% of T-II (n = 18), 65% of T-III (n = 17) and 100% of T-IV (n = 10) and T-V (n = 16) boys. PSA levels rose significantly according to stage (P < 0.05). Also, there were significant (P < 0.05) increments in serum testosterone, IGF-I and IGFBP-3 levels from stages T-I to T-IV. PSA showed a positive correlation with testosterone (r = 0.86, P < 0.001), IGF-I (r = 0.66, P < 0.001), and IGFBP-3 (r = 0.34, P = 0.004) levels. Both PSA and these analytes, however, showed significant overlap between stages T-I and T-II with only 6/18 (33%) and 12/18 (66%) of T-II subjects having PSA and testosterone levels, respectively, above the T-I range. In contrast, serum SHBG levels decreased markedly from stages I to II (P < 0.001). At the calculated best cut-off point for SHBG of 50 nmol/l, 16/18 T-II subjects had values below the T-I range (sensitivity = 89%). Because of this decrement of SHBG and the increasing testosterone secretion in early puberty, the Free Androgen Index (FAI = Testosterone/SHBG) could even better differentiate the onset of puberty with all except one of the T-II subjects having FAI levels above the T-I range (sensitivity = 94.4%). The decrease of SHBG in T-II subjects coincided with an increase in total body weight (P = 0.001) and body mass index (BMI, P = 0.0003). Despite the continuing pubertal rise in testosterone, SHBG levels showed a rebound increment from T-II-T-III subjects (P = 0.02) with a concomitant decrease in BMI (P = 0.0014). CONCLUSIONS: Prostate specific antigen closely reflects serum free androgen activity during puberty. However, it was unable to differentiate the earliest pubertal development. In comparison, SHBG levels and Free Androgen Index are more sensitive markers for the onset of puberty in boys. The inverse association between SHBG levels and BMI in pubertal stages Tanner stages, I to III suggests that body fatness, via its effect on insulin sensitivity, may play an important role in the regulation of SHBG production during early pubertal development.

Adolescent↗
PubMed1975

Luteinizing hormone and androgens in the bovine fetus after gonadotropin-releasing hormone.

After an intra-arterial injection of 10 mug GnRH into four bovine male fetuses, serum LH increased (P less than 0.01) 2-fold by 15 min and plateaued at approximately 11 ng/ml from 60 to 180 min. After GnRH in six female fetuses, LH increased (P less than 0.01) 7-fold by 15 min and plateaued at approximately 17 ng/ml from 60 to 180 min. Maternal serum LH was not significantly influenced (P greater than 0.05) by sex of fetus or administration of GnRH to the fetus. After GnRH in male fetuses, serum testosterone increased (P less than 0.05) and remained 2-fold greater than basal levels through 180 min. In contrast, serum testosterone from female fetuses averaged 370 +/- 60 pg/ml at injection and was unchanged after GnRH. Androgen synthesis was significantly increased during in vitro incubation of fetal testicular explants by the addition of LH. We conclude that GnRH causes release of LH from the bovine fetal pituitary as early as 120 days of age and that the testes respond with testosterone secretion after LH stimulation.

Androstenedione↗
PubMed1979

Prediction of serum testosterone before and after an exercise program using physiological and personality variables.

This study investigated the relationships between serum testosterone level and selected physiological and personality variables in 58 males (21-61 years) before and after a four month physical fitness program consisting of jogging, calisthenics, and recreational activities. Physical fitness scores were obtained for each subject using a regression equation. Serum testosterone was determined using a radioimmunoassay technique. The multiple correlation was used to determine the relationship between serum testosterone and 19 independent variables consisting of age, height, and weight, and percent lean body weight, systolic and diastolic blood pressures, ten factors from the Cattell 16 PF and the three scales of the Eysenck Personality Inventory. A stepwise linear regression was used to identify the predictive power of each of the independent variables. The subjects improved significantly in physical fitness (p < 0.01). The multiple correlations both at the pre-test (R=0.77; R2=0.59) and post-test (R=0.67; R2=0.46) were significant at the 0.01 level. Neuroticism, factors dealing with emotional stability, aggression, and intelligence were powerful predictors initially. Similar results were obtained at the post-test except for the addition of percent lean as a powerful predictor and the absence of factors dealing with intelligence and aggression. The emergence of percent lean was seen to reflect changes in body composition associated with testosterone secretion. The absence of aggression at the post-test was interpreted in light of free catecholamine excretion associated with habitual exercise.

Adult↗
PubMedDate not supplied

The effect of clomiphene citrate and its Zu or En isomers on the reproductive system of the immature male rat.

The effect of clomiphene citrate (CC) and of its Zuclomiphene (ZuC) and Enclomiphene (EnC) isomers on the reproductive organs of immature male rats under different experimental conditions is reported. CC, ZuC, and EnC were administered daily to groups of either intact or castrated rats between the age of 21-44 d. This led to inhibition of weight increase of testis and accessory glands in the intact group. Spermatogenesis was arrested at the stage of primary spermatocyte following CC and ZuC treatment, and at the stage of young spermatids by EnC treatment. In the castrated group clomiphenes significantly stimulated weight increase of seminal vesicles (SV) compared with castrated control animals, but the former group were unable to achieve organ weight gain comparable to that in normal controls. Administration of human Chorionic Gonadotropin (hCG) together with CC or each of its isomers to intact animals, abolished the drug effect on spermatogenesis and on reproductive organ growth. Administration of CC, ZuC, and EnC together with testosterone to castrated animals, abolished the drug effect on growth inhibition of accessory glands. In intact treated rats LH and testosterone secretion were suppressed by all forms of clomiphenes. In the castrated group ZuC proved to be the most potent inhibitor of LH secretion. Therefore, it is inferred that ZuC and EnC have different potencies as far as their biological activity in the immature male rat is expressed.

Animals↗
PubMed1990

The effect of arginine-vasotocin on the production of steroid hormones by mouse, cow, and chicken ovarian tissues in vitro.

The effect of arginine-vasotocin (50 ng ml-1) on the in vitro production of progesterone, testosterone, and oestradiol by isolated cow and chicken ovarian follicles and mouse ovaries was studied. This peptide (1) enhanced the release of progesterone into the medium by the ovarian tissues of all three species of animal; (2) inhibited the production of oestradiol by mouse and cow ovaries; (3) had no significant effect on testosterone secretion in any of the species studied. The results obtained indicate that arginine-vasotocin directly influences steroid production in mammalian and avian gonads.

Animals↗
PubMed1998

The role of parasite-induced immunodepression, rank and social environment in the modulation of behaviour and hormone concentration in male laboratory mice (Mus musculus).

Peripheral immune responsiveness in male laboratory mice was reduced by infection with the trichostrongyloid nematode Heligmosomoides polygyrus. Responsiveness was also lower among high-ranking (aggressive) males regardless of infection status. Reduced responsiveness in both infected animals and high rankers was associated with elevated serum corticosterone concentration (a potential immunodepressant) and was compounded among high-ranking males by subsequent high aggressiveness. As in previous experiments, only low rankers modulated testosterone secretion in relation to current immunocompetence and corticosterone concentration. The lack of any downregulation of aggression in response to parasite-induced immunodepression contrasted with previous results using antithymocyte serum and may be due to the more localized nature of immunodepression during H. polygyrus infection. However, the additional increase in corticosterone concentration resulting from exposure to female odour and destabilized aggressive social relationships did result in downregulation of aggression among high rankers and of testosterone among mice generally, suggesting that modulation rules of thumb are at least partly dependent on the proximate cues associated with immunodepression.

Animals↗
PubMed1990

Effect of hCG or hCG+ treatments in young thalassemic patients with hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism (HH) is common (40%) in beta-thalassemic patients. Taking into consideration that in HH non-thalassemic patients we obtained good results in pubertal development using hCG treatment (1500 IU every 6 days), 10 HH thalassemic subjects (14 5/12 -17 yr, all with bone age greater than 13 6/12) were treated with the same regimen. In 5 of these patients purified FSH (75 IU every 3 days) was added to hCG in order to evaluate the FSH effect on testosterone (T) response (Group 1 was given hCG alone, Group 2 hCG + FSH: Profasi HP and Metrodin Serono). To evaluate the kinetics of testosterone response, plasma level of T was determined basally and 1, 2, 4 and 6 days after hCG injection. This dynamic study and a clinical examination were carried out at the beginning of treatment and at the 4th and 12th month after. Results obtained in the first group confirmed our previous data from non-thalassemic HH patients: in fact, after 12 months of therapy a stage G2-G3 was reached. In the second group, however, testis size and testosterone secretion were significantly higher than in the first group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Neonatal exposure of female ferrets to testosterone alters sociosexual preferences in adulthood.

Sociosexual preferences in adult female ferrets, as measured in a choice arena, were altered by neonatal exposure to exogenous testosterone. Adult female ferrets showed a preference for males which did not depend on the presence of gonadal steroids, because gonadectomized and gonadectomized estrogen-treated females showed identical preferences for males. Adult castrated males showed no preference for females unless these males were treated with testosterone. A similar no-preference pattern was found in adult females that had received testosterone neonatally. Females exposed neonatally to dihydrotestosterone or estradiol exhibited the normal females' male-oriented preference. These results indicate that testosterone secreted by the testes in the developing male may interrupt the phenotypic female development pattern and hence prevent the emergence of a homosexual preference in adulthood in the male ferret.

Animals↗
PubMed1986

Photoperiod, follicle-stimulating hormone receptors, and testicular function in vizcacha (Lagostomus maximus maximus).

In the present work we investigated the presence of testosterone in serum and follicle-stimulating hormone (FSH) receptors in testes of the vizcacha (Lagostomus maximus maximus), a South American rodent. We also investigated the effect of constant light on both parameters. The control group consisted of vizcachas caught in their natural habitat and maintained under continuous darkness; the experimental group consisted of animals maintained under constant light (1076 lx) for 8 days. The results revealed a significant decrease in serum testosterone and FSH receptors when the animals were maintained under constant light, as compared to the control group. Androstenedione was elevated in the serum obtained from the experimental group. It is postulated that the pineal gland may regulate testosterone secretion through FSH receptors and through an enzymatic blockade in the steroidogenic pathway; this supposition, however, remains to be proved.

Androstenedione↗
PubMed1991

Does unilateral orchidectomy influence blood flow, microcirculation and vascular morphology in the remaining testis?

Adult rats were hemi-orchidectomized and various aspects of testicular blood flow, microcirculation and vascular morphology were studied in the remaining testis after 30 days and compared to that in intact sham-operated animals. Testis weight, total testicular blood flow (measured with microspheres), capillary blood flow pattern (studied with laser Doppler flowmetry) and the volume of interstitial fluid in the testis (index of vascular permeability) were all unaffected by hemi-orchidectomy. Morphometric measurements on perfusion-fixed testicular tissue showed that the volume densities of Leydig cells, blood vessels and small exchange blood vessels were increased by hemi-orchidectomy (by approximately 45, 33 and 42%, respectively). The volume density of Leydig cells in individual testes was correlated to the volume and surface density of capillaries + small postcapillary velules (r = 0.72 and 0.86, respectively). Hemi-orchidectomy is known to result in a doubling in testosterone secretion per Leydig cell. This increased endocrine activity results in moderate increase in the vascular exchange area but other aspects of testicular microcirculation and blood flow are apparently unaffected.

Animals↗
PubMed1983

Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases.

Four boys with sexual precocity are described in whom pubertal concentrations of plasma testosterone were associated with premature Leydig and germinal cell maturation without activation of the hypothalamic-pituitary gonadotropin unit. Extensive laboratory evaluation localized the source of testosterone secretion to the testes, and testicular biopsy revealed maturation of Leydig cells and spermatogenic elements. These events appear to be nongonadotropin-dependent in view of the absence of a pubertal pattern of pulsatile LH secretion, persistence of a prepubertal LH response to LRF even after long standing sexual precocity, prepubertal basal levels of LH and undetectable hCG, and the absence of biologically active LH-hCG by bioassay. Indirect immunofluorescence studies failed to demonstrate an immunoglobulin in the patients' sera that bound to Leydig cells or seminiferous tubules of normal adult human testes. The potent LRF analog D-Trp6-Pro9-NEt-LRF did not result in suppression of plasma testosterone or Leydig cell function even after 3 months of daily treatment in two patients which provides additional support of pituitary gonadotropin independence and of the lack of a direct effect of the analog on Leydig cell function. Oral medroxyprogesterone acetate treatment in two patients was associated with a striking decrease in both plasma testosterone concentration and height velocity. In the only patient in whom a complete family history could be obtained (three of four patients were adopted), sexual precocity was noted in the maternal grandfather. As this familial syndrome is characterized by a prepubertal hypothalamic-pituitary gonadotropin unit and apparent gonadotropin-independent maturation of Leydig cells and germinal epithelium, possibly due to an intratesticular inborn error, we propose the term "familial testotoxicosis" to describe this group of sexually precocious boys.

Child, Preschool↗
PubMed2003

[Serum levels of luteinizing hormone, testosterone and prolactin in patients with septic shock].

Many studies show important disturbances in hormonal balance in patients with severe sepsis. There are a lot of factors, which are involved in this process but the role of sex steroid hormones is unknown; especially, the role of testosterone, which is one of the anabolic hormones and a immune function modulator. We hope that sex steroid hormone mechanisms of action recognition in septic shock may help in treatment of such patients. The aim of this study was to evaluate changes in sex hormone concentrations in septic patients and their prognostic significance. We studied serum level of luteinizing hormone (LH), testosterone (T) and prolactin (PRL) in 20 patients with septic shock and in healthy male volunteers (n = 20). Septic patients were divided into two groups: survivors (group I, n = 10) and nonsurvivors (group II, n = 10). We noticed significant decrease of testosterone and LH serum levels in septic group vs the controls and correlation between T and LH serum levels and survival. Acute lung injury was associated with higher PRL serum level and was independent from the LH and T serum level. We also noticed incorrect pituitary down-regulation of testosterone secretion. Our study showed that sex steroid hormones can be good prognostic factors of survival and complications of septic shock.

Adult↗
PubMed2007

Reduced aggression in mice lacking GABA transporter subtype 1.

Dysregulation of the brain GABAergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central GABAergic activity, dysfunction of the GABA transporter subtype 1 (GAT1) represents a potential mechanism mediating pathologic aggression. We provide evidence that GAT1-/- mice and GAT1+/- mice exhibit lower aggressive behavior both in home cage resident-intruder test and neutral arena resident-intruder test, compared to wild-type mice (GAT1+/+). The pharmacologic effects of the GAT1 inhibitor, tiagabine and the GABA(A) receptor antagonist, bicuculline have been assessed in GAT1+/+ mice: tiagabine inhibits attacks but bicuculline induces attacks. Compared to GAT1+/- and +/+ mice, the GAT1-/- mice displayed a normal circadian pattern of home cage activity, but more activity overall. Meanwhile, reduced testosterone concentration was found in GAT1-/- mice compared to GAT1+/+ mice but not in GAT1+/+ mice treated with tiagabine, suggesting that testosterone is not directly involved in GAT1 mediated aggressive behavior regulation. These results showed that GAT1 is an important target involved in the regulation of aggressive behavior in mice, and long-term dysfunction of GAT1 may also result in the alteration of testosterone secretion.

Aggression↗
PubMed2004

Effect of undegradable protein supply on testicular size, spermiogram parameters and sexual behavior of mature Assaf rams.

Eighteen mature Assaf rams were used to study the effect of undegradable protein (UDP) supply on testicular size, sperm production and quality, testosterone secretion and reproductive behavior. Animals were allocated to three groups of six animals each and fed during 10 weeks with different diets which were designed to supply approximately 0.5MJ of metabolisable energy (ME)/kg LBW(0.75) and 9g of effective rumen degradable protein (ERDP)/MJ of fermentable ME to all animals and to induce differences in rumen UDP intake (0.97, 1.72 and 3.08g of UDP/kg LBW(0.75) for LP, MP and HP diets, respectively). Neither plasma testosterone concentration nor reproductive behavior parameters (number of services, number of mounts without ejaculation and reaction time to first mount) were affected (P > 0.05) by protein intake. Nevertheless, there were significant (P < 0.05) differences between diets in both testicular size and sperm production. Scrotal circumference was lower in LP compared to MP and HP groups, no significant differences being observed between these latter two groups at any time. In relation to sperm production, the lowest and the highest values were always observed in LP and HP groups, respectively. MP group showed intermediate values, significantly different from those of LP and HP groups on Week 5 and only from those of LP group on Week 9. The present results provide a better understanding of the effect of protein nutrition and suggest that UDP should be supplied to Assaf rams during the mating season to improve their reproductive performance.

Animal Nutritional Physiological Phenomena↗