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PubMed1983

Active immunization with follicle-stimulating hormone for fertility control: a 4 1/2-year study in male rhesus monkeys.

Active immunization of four adult rhesus monkeys with highly purified ovine follicle-stimulating hormone (FSH) over 4 1/2 years resulted in the production of specific FSH antibodies. While luteinizing hormone and testosterone secretion were not affected, sperm counts were in most instances reduced to or below the lower normal range. On a few occasions, azoospermia or high sperm counts were observed. Although the antibodies produced neutralized the biologic activity of FSH throughout, spermatogenesis gradually returned, as evidenced by testicular histologic characteristics. However, the diameter of the seminiferous tubules remained decreased, and the germinal epithelium was depleted. No adverse side effects could be demonstrated in the immunized animals, e.g., immune complexes in either serum or tissues and resultant tissue damage. These results show that although active immunization with FSH may not result in an effective method of male fertility control, long-term immunization against a circulating hormone may not result in deleterious side effects.

Animals↗
PubMed1982

Testicular atrophy associated with agenesis of the epididymis in the ACI rat.

The male ACI rat has a congenital Wolffian duct defect manifested by unilateral agenesis of the kidney, ureter, seminal vesicle, ductus deferens, and most of the epididymis. In the adult the testis on the affected side is markedly smaller than the contralateral testis and spermatogenesis is absent. In addition, in vitro perfusion of the affected testis revealed significantly less testosterone secretion than did the contralateral testis. Moreover, electron microscopy revealed that the smooth endoplasmic reticulum of the Leydig cell was significantly decreased. Thus, the affected testes clearly showed deranged spermatogenesis and Leydig cell structure and function. The ACI rat model may provide insight into the potential effects of congenital epididymal abnormalities on the testis of the human.

Animals↗
PubMed2001

Ramadan fasting alters endocrine and neuroendocrine circadian patterns. Meal-time as a synchronizer in humans?

Muslims must refrain from eating, drinking, smoking, and sexual relations from sunrise to sunset during the month of Ramadan. Serum concentrations of melatonin, steroid hormones (cortisol, testosterone), pituitary hormones (prolactin, LH, FSH, GH, TSH) and thyroid hormones (free thyroxin and free triiodothyronine) were documented around the clock at six 4-hourly intervals before Ramadan began and on the twenty-third day of Ramadan (daytime fasting). Time series were analysed with repeated measures ANOVA. Statistically significant differences were found in some variables: the nocturnal peak of melatonin was diminished and may have been delayed; there was a shift in the onset of cortisol and testosterone secretion; the evening peak of prolactin was enhanced, FSH and GH rhythmic patterns were affected little or not at all by Ramadan fasting and only the serum TSH rhythm was blunted over the test time span. These data show that daytime fasting, modifications in sleep schedule and psychological and social habits during Ramadan induce changes in the rhythmic pattern of a number of hormonal variables.

Adult↗
PubMed1996

Influence of early postnatal gonadal hormones on anxiety in adult male rats.

Behavioral sex differences have been linked to the presence of testosterone secretion during a critical perinatal period. The present experiment tested whether or not castration at different ages (early postnatal period and adulthood) would alter performance in the plus maze, a behavioral test of anxiety. Intact adult male rats (n = 17) were compared to intact adult females (n = 17); adult castrated males (n = 7) to sham-operated adult male rats (n = 9); and newborn castrated males (n = 7) to sham-operated male offspring (n = 8). When adult, the subjects were left on an elevated plus maze for 5 min. Females made a higher percentage of entries onto the open arms and showed a greater number of scans over the edge of an open arm than males. There were no differences in the percentage of arm entries or time spent on the open arms when adult castrated males were compared to sham-operated rats. On the other hand, newborn castrated males showed a significantly higher number of open arm entries and spent a greater percentage of time on the open arms than sham-operated offspring. The results demonstrate that the absence of male gonadal hormones during the perinatal period decreases anxiety, as assessed in the elevated plus maze, leading to a behavioral pattern that resembles that of females. These data provide evidence for the organizational role of gonadal hormones in the development of behavioral inhibitory systems.

Animals↗
PubMed1998

Testicular denervation-induced nuclear changes in Leydig cell of hemicastrated adult rats.

In the adult male rat, hemicastration (HC) induces a remarkable enhancement of testosterone secretion from the Leydig cells of the remaining testis. We have observed previously that the denervation of inferior spermatic nerves inhibits this enhancement. The present experiments were designed to assess morphometrically whether or not this change had a cytological correlate in Leydig cells. At least five testes from each group (denervation plus HC, sham denervation plus HC and intact rats) were prepared for both optical and electron microscopy studies. The results showed that after 24 h of denervation, the nuclear volume of the Leydig cells in denervation plus HC rats was smaller (p < 0.01) than those of sham denervation plus HC (196.56 +/- 16.53 vs. 280.71 +/- 13.37), whereas both the volume density of heterochromatin (19.84 +/- 3.14 vs. 10.03 +/- 2.47%) and the heterochromatin index (expressed as periphery heterochromatin area divided by nuclear perimeter, 0.149 +/- 0.046 vs. 0.094 +/- 0.026) were significantly (p < 0.01) higher in denervation plus HC rats than in its sham groups. No changes in Leydig cell numbers or cytoplasmic organelles were detected. The results suggest that some nuclear and heterochromatin-associated cellular activity might be inhibited by testicular denervation in hemicastrated rats.

Animals↗
PubMed2003

Human chorionic gonadotropin free beta-subunit in the human seminal plasma: a new marker for spermatogenesis?

UNLABELLED: In the past 20 years, several factors were detected in the human seminal plasma and proposed as markers for spermatogenesis. Human chorionic gonadotropin (hCG) and its beta-subunit were therefore investigated, and their seminal levels were found to be higher than those detected in the serum and to correlate with sperm parameters. OBJECTIVE: We designed a retrospective study to determine the suitability of hCG free beta-subunit concentration in the seminal plasma of fertile and infertile male patients as marker of spermatogenesis. STUDY DESIGN: A total of 79 infertile male patients were divided into four groups by their semen analysis results (group 1 [n=8]: azoospermia; group 2 [n=21]: severe oligozoospermia; group 3 [n=40]: oligoasthenospermia (OAS); group 4 [n=10]: asthenospermia) and 10 healthy volunteers of proven fertility were evaluated. RESULTS: The hCG free beta-subunit levels in the seminal plasma were found to be significantly higher (P<0.0001) in the control group in respect to those assayed in the infertile patients and showed a correlation with sperm count (r=0.5) and total motile sperm density (r=0.5). Twenty-five patients were on treatment with oral Mesterolone (100mg daily) plus Tamoxifen (20mg daily) for 3-6 months. Apart from a significant improvement (P<0.05) in sperm morphology, no significant changes in sperm count and motility were observed after the treatment in all the patients. In the seminal plasma of 10 patients who showed a significant increase in sperm count, hCG free beta-subunit levels were found to be significantly higher compared to those detected in the remaining patients (P<0.01). In all patients, these levels remained unchanged after the treatment. CONCLUSIONS: The evidence regarding the positive correlation between hCG free beta-subunit levels in the seminal plasma and sperm concentration is consistent with the previous results regarding hCG levels. A previous study demonstrated that testosterone levels in seminal plasma correlated with sperm concentrations; from the same evidence regarding hCG we hypothesize that seminal plasma testosterone and hCG levels are correlated. Thus, hCG may play a paracrine role in the intratesticular regulation of testosterone secretion.

Adult↗
PubMed2000

Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers.

To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin were determined, and area-under-the-curve values were calculated. None of the endocrinological parameters revealed any statistically significant changes. A trend could be found for an increased cortisol production under paroxetine (P = 0.069). ACTH, LH, and melatonin showed slight and non-significant decreases. Prolactin release was only marginally elevated (+7%). The mean sleep onset GH release (as measured for a time period of 180 min after sleep onset) was decreased by about 30% under paroxetine. However, statistical significance could not be reached. For hGH, there was a delayed mean GH-peak under paroxetine. Nocturnal testosterone secretion remained almost unaltered. The lack of significant endocrinological alterations might be partially explained by both adaptational phenomena under subchronic treatment conditions and the extended time span between the single morning dose and the registration period, respectively.

Adrenocorticotropic Hormone↗
PubMed1997

Experimental analysis of sexual differentiation of the zebra finch brain.

Classical theories of sexual differentiation of brain and behavior hold that sex differences in the brain arise because of the action of gonadal steroid hormones. In mammals, testosterone secretion by the testes stimulates a masculine pattern of neural differentiation, whereas feminine patterns of development occur in the absence of testicular secretions. In some bird species, estrogen secreted by the ovary is thought to trigger feminine patterns of neural development, whereas masculine development occurs in the absence of ovaries. Sexual differentiation of the neural circuit for song in zebra finches is not easily explained by these theories. Although female zebra finches can be masculinized by treatments with estrogen, it has proven difficult to prevent masculine neural development in genetic males by treating them with inhibitors of estrogen synthesis. Moreover, when genetic female embryos are treated with inhibitors of estrogen synthesis, they develop significant amounts of testicular tissue that causes little or no masculinization of the song system. Thus, testicular secretions alone appear to be insufficient to cause masculine neural differentiation, and other factors need to be invoked. These factors may include ovarian secretions that inhibit masculine development, or direct genetic (nonhormonal) effects on neural differentiation.

Animals↗
PubMedDate not supplied

2-Bromopropane induces DNA damage, impairs functional antioxidant cellular defenses, and enhances the lipid peroxidation process in primary cultures of rat Leydig cells.

Utilization of highly enriched preparations of steroidogenic Leydig cells has proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. It is widely reported that male reproductive organs are particularly susceptible to the deleterious effects of reactive oxygen species (ROS) and lipid peroxidation, which ultimately lead to impaired fertility. The purpose of the study was to examine the potential of 2-bromopropane (2-BP) to induce oxidative stress and antioxidant function in primary cultures of rat Leydig cells. Leydig cells were isolated from the testes of Sprague-Dawley rats. The purity of Leydig cells was determined to be 94.6% and the cells maintained their testosterone secreting capabilities for 48 h. Fresh medium containing 2-BP (1.00, 0.10, 0.01 mM, and vehicle control) and 1 U human chorionic gonadotropin (hCG) were added in the cell culture. Superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) were analyzed in the medium of each well by biochemical methods. Additionally, DNA damage was examined using the Comet assay. The proportion of cells with undamaged DNA was decreased significantly and those with different grades of damaged DNA were increased significantly in the cells exposed to 2-BP. The level of MDA and GSH-PX activity increased significantly in the cell groups exposed to 0.10 and 1.00 mM 2-BP, whereas, SOD activity decreased considerably in these two groups of cells when compared to the control. The data indicate that 2-BP induces DNA damage, impairs functional antioxidant cellular defenses, and enhances the lipid peroxidation in cultured Leydig cells. These effects may be responsible for the testicular toxicity noted in laboratory animals and humans.

Animals↗
PubMed2002

Avian reproductive anatomy, physiology and endocrinology.

Although many environmental cues influence reproductive activity, the seasonal breeder responds most strongly to long day length. THE MALE BIRD: Testicular interstitial cells secrete testosterone, which influences reproductive behavior such as territorial aggression and song. Other changes observed in seasonal breeders include testicular hypertrophy and enlargement of the ductus deferens and seminal glomus. THE FEMALE BIRD: Early changes associated with rising estrogen levels in the hen include osteomyelosclerosis and hypercalcemia. Ovulation is then induced by LH, which is followed by eggshell calcification, which is under the control of progesterone. Sources of calcium for shell production include intestinal absorption from the diet, renal control of calcium levels, and mobilization of bone calcium stores. During oviposition, PGF2 alpha and vasotocin stimulate powerful uterine contractions [32] in the presence of calcium. Incubation is associated with falling LH levels and rising prolactin levels. If the hen actually enters reproductive quiescence at this time, then molt will follow. Molt is associated with the total regression of the reproductive tract.

Animals↗
PubMed1998

Endocrine therapy of transsexualism and potential complications of long-term treatment.

Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sex hormonal therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sex hormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used.

Adolescent↗
PubMed2000

Sexual differentiation.

Sexual differentiation in humans is genetically and hormonally controlled. In response to a signal from a dominant-acting gene on the Y chromosome, primordial cells in the embryonic gonad ridge differentiate into Sertoli cells and affect newly migrated germ cells to differentiate as spermatogonia, thus creating a testis. The cells of the embryonic testis secrete hormones that lead to the development of most, if not all, male secondary sexual characteristics. The Sertoli cells secrete müllerian inhibitory factor (MIF), causing regression of the müllerian ducts and of stray oogonia. The Leydig cells secrete testosterone, causing differentiation and growth of the wolffian duct structures. Dihydrotestosterone, created by metabolism of testosterone, causes growth of the prostate and phallus and fusion of the labioscrotal folds. In the absence of SRY, Sertoli cell differentiation does not occur. Rather germ cells migrating into the primordial gonad differentiate as oogonia and cause interstitial cells to differentiate as granulosa cells. In the absence of MIF and testosterone, the müllerian ducts differentiate and grow as female internal genitalia and the external genitalia are feminized. Several genes have been identified that control testis determination. These include SRY, WT1, SOX9, SF1, XH2, and DAX1. Most of these genes were discovered by analysis of rare cases of sex reversal (genetic sex of one type, gonadal sex of the other type).

Cell Differentiation↗
PubMed1988

Effect of organophosphorus (dimethoate) and pyrethroid (deltamethrin) pesticides on semen characteristics in rabbits.

The present study was undertaken to determine the effect of chronic treatment with two sublethal doses of Dimethoate (organo-phosphorus) or Deltamethrin (pyrethroid) on body weight and semen characteristics in adult male rabbits. Pesticide treatment resulted in a decline in body weight, libido, ejaculate volume, sperm concentration and semen initial fructose; and an increase in abnormal and dead sperm and methylene blue reduction time. In this regard Dimethoate showed greater effects than Deltamethrin. The hazardous effect of these pesticides on semen quality continued during the post-treatment period, and was dose-dependent. This deleterious effect on sperm formation together with the decline in libido suggest a decrease in testosterone secretion by pesticide treatment.

Animals↗
PubMed1960

Estradiol reduces incorporation of radioactive sulfate into cartilage and aortas of rats.

Estradiol in large amounts reduces the incorporation of radioactive sulfate into cartilage and aortas of rats. This reduction becomes apparent within 3 days for cartilage and 3 weeks for aorta. The effect is not mediated through suppression of testosterone secretion and the hypophysis is not necessary for the effect to be demonstrated. The thoracic segment of aortas from normal rats incorporates more sulfate than does the abdominal segment and this difference is reduced following the administration of estradiol.

Animals↗
PubMed1997

Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia.

Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX patients have experienced spontaneous pubertal changes including breast development and irregular menstruation whereas none of the 46,XY subjects displayed pubertal changes. Eight different mutations were identified. Sixteen patients were either homozygotes or compound heterozygotes for the Q258X mutation. The seven other mutations identified were 189delG, 246insG, 564del13bp, 838delA, Q212X, A218V and M225T. The 189delG, 246insG, 546del13bp and Q212X mutants encode truncated proteins. COS-1 cells transfected with expression vectors encoding cDNAs for the mutant StAR proteins which affect the C-terminus, 838delA, A218V and Q258X, exhibited no steroidogenesis enhancing activity. However, the M225T mutant retained some steroidogenic activity. The patient with the M225T mutation had late onset of this disorder and some capacity to secrete testosterone in response to hCG. These findings suggest: (i) that the Q258X mutation can be used as a genetic marker for the screening of Japanese for lipoid CAH, (ii) that the C-terminus of StAR plays an important role in the protein's activity and (iii) that there are differences in the extent of functional impairment of the testis and ovaries in lipoid CAH.

Adrenal Hyperplasia, Congenital↗
PubMed2001

Long-term effects on male reproduction of early exposure to common chemical contaminants in drinking water.

We evaluated sequelae to early exposure of male rabbits to drinking water containing chemicals typical of ground water near hazardous waste sites. The mixture (p.p.m. at 1x) was 7.75 arsenic, 1.75 chromium, 9.25 lead, 12.5 benzene, 3.75 chloroform, 8.5 phenol and 9.5 trichloroethylene. Dutch-Belted does received mixture at 0x (deionized water; control), 1x or 3x as drinking water from day 20 pregnancy through weaning. Exposure of individual males (7-9/treatment) continued until 15 weeks (adolescence); then, all males received deionized water. At 57-61 weeks of age, ejaculatory capability and seminal, testicular, epididymal and endocrine characteristics were evaluated. At 10 opportunities with a female teaser, all seven control males ejaculated every time, but 12 of the 17 treated males failed to express interest, achieve erection and/or ejaculate on one to five occasions; four of the 12 accomplished ejaculation with a second male teaser. Total spermatozoa/ejaculate and daily sperm production were unaffected. However, treatment caused (P < 0.03) acrosomal dysgenesis and nuclear malformations. Baseline serum concentrations of LH were lower, but with borderline significance (P = 0.05). Testosterone secretion after exogenous human chorionic gonadotrophin (P < 0.04) was low. Thus, even at 45 weeks after last exposure to drinking water pollutants, mating desire/ability, sperm quality, and Leydig cell function were subnormal.

Animals↗
PubMed2001

Ovarian and endometrial function during hormonal contraception.

This report addresses the balance of benefits and risks from changes in ovarian and endometrial function from hormonal contraception. The main mode of action of hormonal contraception is inhibition of ovulation, due chiefly to the dose of oestrogen in combined oral contraceptives. With 20 microg dosages of ethinyl oestradiol follicular activity is more common so that contraception depends on suppression of the LH surge or disruption of the endometrial cycle. In polycystic ovary syndrome (PCOS) treated with oral contraceptives, cysts become smaller and in time the ovarian volume is reduced, ovarian testosterone secretion is reduced and there are potentially favourable effects on carbohydrate and lipid metabolism. Typical oral contraceptive users in the 1980s had a lower incidence of ovarian cysts, but modern oral contraceptives do not appear to affect the incidence of functional cysts or benign epithelial cysts. Moreover, randomized controlled trials indicate that oral contraception prescriptions are unlikely to prevent the development of functional cysts or to hasten their disappearance. Oral contraceptives, however, greatly reduce pelvic pain in women with symptomatic endometriosis and improve the health-related quality of life. Bleeding is a common response with all types of hormonal contraception, but current methodology is inadequate to make accurate comparisons of different products or of different phasic formulations. With continuing use, however, combined oral contraception is associated with endometrial atrophy, the biological plausibility for a reduced risk of endometrial carcinoma. With progestin-only contraception, a number of endometrial changes are considered as possible mechanisms of the associated bleeding but it remains largely unexplained. Oral contraceptives are frequently used for treatment of dysfunctional uterine bleeding, although only one trial has been reported. Oral contraceptive use confers protection from endometrial [relative risk (RR) 0.5] and ovarian (RR 0.4) cancers and in both cases, the protection lasts for up to 2 decades after stopping use.

Contraceptive Agents, Female↗
PubMed1984

Influence of adenosine 3':5'-cyclic monophosphate analogues on testicular organization of fetal mouse gonads in vitro.

Gonadal primordia, isolated from fetal mice on the 11th or 12th day of gestation, differentiated in vitro into morphologically distinct testes or ovaries after 7 days in culture. The addition of cAMP analogues into culture media prevented the differentiation of testis cords. Histological examination indicated that the basement membranes of testis cords disintegrated after treatment with cAMP analogues, while development of germ cells and Leydig cells appeared to be unaffected. Fetal testes in culture secreted testosterone which increased following addition of dibutyryl-cAMP (Bt2 c-AMP). Primordial germ cells reached prespermatogonial stage in the presence or absence of Bt2 cAMP, suggesting that progressive differentiation of primordial germ cells is independent of testis cord organization. The Bt2 cAMP-treated explants resumed testicular development after transplantation into a site beneath the kidney capsules of adult mice, although the inhibitory effect appeared irreversible in vitro. The testicular organization-preventing effect of cAMP analogues was mimicked by prostaglandins or forskolin, which are known to stimulate adenylate cyclase. The inhibitory effect of either cAMP analogues or prostaglandins was potentiated when added in combination with phosphodiesterase inhibitors. The present results suggest that increase of intracellular cAMP prevents the development of basement membrane and the assembly of cells to form testicular structures.

8-Bromo Cyclic Adenosine Monophosphate↗