Higher Serum Testosterone Levels Research Articles

Association Between Serum Sex Hormone Levels and Prostate Cancer: Effect of Prostate Cancer on Serum Testosterone Levels

Androgens are essential for prostatic growth and development, but also play a significant role in the pathogenesis of prostate disease. The traditional view that higher testosterone levels represent a risk factor for prostate cancer (PCa) appears to have little evidentiary support. Some studies have described a relationship between lower testosterone levels and more advanced disease. Serum androgen levels, within a broad range, are thus suggested to show no association with PCa risk, whereas low rather than high serum testosterone levels have been found to be associated with advanced or high-grade disease at the time of PCa diagnosis. Dihydrotestosterone, the principal prostatic androgen, is transformed from testosterone by type 1 and type 2 5alpha-reductase, and therapeutic benefits may thus be potentially achieved through the inhibition of 5alpha-reductase.

Associations of Anthropometric Parameters with Serum TSH, Prolactin, IGF-I, and Testosterone Levels: Results of the Study of Health in Pomerania (SHIP)

Obesity is a major risk factor for chronic diseases including cardiovascular disorders. Divergent associations between obesity and hormonal changes have been reported. The objective of the present study was to analyse the associations between anthropometric measurements and hormone levels including serum thyroid stimulating hormone (TSH), prolactin, insulin-like growth factor (IGF) I, and testosterone. Form the cross-sectional Study of Health in Pomerania 1 women and 1 864 men aged 20-79 years were included in the analyses. Serum TSH, prolactin, IGF-I, and testosterone levels were determined by immunochemiluminescent procedures. Body height, weight as well as waist and hip circumferences were measured. Body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were calculated. Our analyses revealed inverse linear associations of waist and hip circumferences, BMI and WHtR with serum TSH levels and linear associations between waist circumference as well as WHtR and serum prolactin levels in women. In men, inverse linear and quadratic associations between anthropometric parameters and serum IGF-I as well as serum testosterone levels were found. Additionally, men with high waist circumference had more often low serum IGF-I or testosterone levels and less often high serum IGF-I or testosterone levels compared to men with low waist circumference. These sex-specific differences should be noted in studies regarding hormones and obesity.

Prolactin and pituitary-gonadal function in cigarette smoking infertile patients.

Serum prolactin (PRL) was significantly lower in smokers, compared with non-smokers in 233 males and 250 females referred to our infertility clinics. In subjects smoking 10 cigarettes or more per day, the mean serum PRL was 22% and 20% lower in men and women, respectively. In cigarette smoking men serum testosterone was significantly higher and semen volume lower, while neither serum luteinizing hormone (LH) or follicle stimulating hormone (FSH), sperm density, motility of morphology differed between smokers and non-smokers. It is possible that the higher serum testosterone levels in smokers are due to their lower bodyweight, and that the lower semen volume may be due to an effect of nicotine on the contractility of the deferental ducts. Cigarette smoking may increase central dopaminergic tonus and reduce PRL levels, but it is unknown whether or not this is of biological significance in relation to reproductive function.

High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men

Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis (EE) secondary to hypoventilation. Erythropoietin (Epo) and testosterone regulate erythrocyte production. Low thyroid hormone levels are also associated to hypoventilation. Hence, these hormones can play a role in etiopathogeny of EE. The purpose of this study was to elucidate the effect of sexual and thyroid hormones and Epo in residents from Lima (150 m) and Cerro de Pasco (4,340 m), Peru, and the response to human chorionic gonadotrophin stimulation (hCG). Three groups, one at low altitude and two at high altitude [1 with hemoglobin values >16-21 g/dl and the second with Hb >or=21 g/dl (EE)], were studied. hCG was administered intramuscularly in a single dose (1,000 IU), and blood samples were obtained at 0, 6, 12, 24, 48, and 72 h after injection. High-altitude natives present similar levels of gonadotropins and thyroid hormones but lower dehydroepiandrosterone sulphate (DHEAS) levels (P < 0.01) and greater Epo (P < 0.01), 17alpha-hydroxyprogesterone (P < 0.01), and testosterone levels (P < 0.01) than those at 150 m. Serum testosterone levels (524.13 +/- 55.91 microg/dl vs. 328.14 +/- 53.23 ng/dl, means +/- SE; P < 0.05) and testosterone/DHEAS ratios are higher (7.98 +/- 1.1 vs. 3.65 +/- 1.1; P < 0.01) and DHEAS levels lower in the EE group (83.85 +/- 14.60 microg/dl vs. 148.95 +/- 19.11 ug/dl; P < 0.05), whereas Epo was not further affected. Testosterone levels were highest and DHEAS levels lowest in the EE group at all times after hCG stimulation. In conclusion, high androgen activity could be involved in the etiopathogeny of CMS. This evidence provides an opportunity to develop new therapeutic strategies.

Virilizing ovarian tumor in a 14‐year‐old female with a prior familial multinodular goiter

A 14-year-old female presented with intermittent abdominal pain, deepening of voice and amenorrhoea for 4 months. Twelve months earlier she had had a thyroidectomy because of familial multinodular goiter and had, subsequently, received substitution with L-thyroxine. At the time of admission, a high serum testosterone level was detected. The dexamethasone suppression test confirmed the hormonal autonomy and magnetic resonance imaging (MRI) visualized a solid tumor within the left ovary. The pathological diagnosis after left salpingo-oophorectomy was Sertoli-Leydig cell tumor. The patient has remained disease-free for 6 years.

The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer

5074 Background: We sought to evaluate the relationship of baseline body mass index (BMI), NIH-defined presence of obesity, and serum testosterone levels with disease-specific outcomes and prognosis in men with castration resistant metastatic prostate cancer (CRPC). Methods: BMI and testosterone level were evaluated for their ability to predict overall survival (OS) and progression-free survival (PFS) in multivariable analysis using data from the TAX327 clinical trial. This was an international phase III randomized controlled trial of one of two schedules of docetaxel and prednisone compared with mitoxantrone and prednisone. BMI and testosterone were additionally examined for prognostic significance in determining PSA declines with chemotherapy as well as the relationship to other prognostic factors. Results: In this study of 1006 men with CRPC, the median serum testosterone level was 14.5 ng/dl (range 0–270), the median BMI was 27 kg/m2 (range 15.7–46.5), and 26% of men were obese or morbidly obese (BMI > 30). Obese men were significantly more likely to be younger, have fewer visceral metastases, lower PSA and alkaline phosphatase, and have higher performance status, primary Gleason sum, testosterone, and hemoglobin levels as compared to non-obese men. In multivariable analysis, neither BMI nor the presence of obesity was significantly associated with PSA declines with therapy, progression-free survival, or overall survival. Baseline testosterone in the castrate range was also not associated with disease outcome, including PSA declines, PFS, or OS. Conclusions: In this multicenter international trial of men with CRPC, neither BMI nor serum testosterone in the castrate range were associated with prostate cancer outcomes. The cut-off threshold for castrate levels of serum testosterone should remain ≤50 ng/dl. Higher levels of serum testosterone among obese men suggest incomplete gonadal suppression with current therapies, but these differences may not be clinically relevant in men with CRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis

Female field voles with high testosterone and glucose levels produce male-biased litters

The proximate physiological mechanisms producing the parental ability to vary offspring sex ratio in many vertebrates remain elusive. Recently, high concentrations of maternal testosterone and glucose and low concentrations of maternal corticosterone have been suggested to explain male bias in offspring sex ratio. We examined how these factors affect secondary offspring sex ratio in nondomesticated field voles, Microtus agrestis, while controlling for maternal age, testosterone level of the male and body condition of both the female and the male. We found that females with high preconception serum testosterone and glucose levels produced a male-biased litter, whereas there was no association between maternal corticosterone level and litter sex ratio. Older females produced a bias towards sons, but neither their body condition nor paternal testosterone level correlated with litter sex ratio. Finally, females mated with a high body-condition male tended to deliver a male-biased litter. Our results suggest that several physiological traits of the mother may simultaneously be related to offspring sex ratio in mammals.

The Influence of High Serum Testosterone Levels on the Long‐term Prognosis in Male Patients Undergoing Hepatectomy for Early Stage Hepatocellular Carcinoma without Vascular Invasion

The influence of high serum testosterone levels on the long-term prognosis in male patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains to be fully elucidated. The aim of the present study was to conduct a retrospective investigation of the impact of high serum testosterone levels on the risk of tumor recurrence and long-term prognosis in male patients undergoing hepatectomy for early stage HCC without vascular invasion. Between August 1995 and March 1999, 42 male patients undergoing curative hepatectomy for HCC of tumor-node-metastasis (TNM) stages I and II without vascular invasion were enrolled in the study. Preoperative serum testosterone concentration was measured. The clinicopathological features, tumor recurrence rates, and 5-year disease-free and actuarial survival after hepatectomy were compared between the patients with serum testosterone levels in the upper half (group I, n = 21) and the patients in the lower half (group II, n = 21). The background and clinicopathological features did not differ significantly between groups I and group II. All survivors were followed up for more than 5 years. Until March 2005, patients in group I, with serum testosterone levels in the upper half, had a significantly higher percentage of 5-year tumor recurrence than group II, with lower testosterone levels (76.2% versus 28.6%; p < 0.005). The patients in group I also had a significantly inferior 5-year disease-free (p < 0.01) and actuarial (p < 0.05) survival rates than patients in group II. Male patients with high serum testosterone levels undergoing hepatectomy for early stage HCC without vascular invasion have significantly higher 5-year tumor recurrence rates and an inferior long-term prognosis than patients with low testosterone levels. These findings signal a strategy of adjuvant anti-androgen treatment selectively targeted for the male patients with high serum testosterone levels after hepatectomy for early stage HCC without vascular invasion to achieve better long-term outcome.

In vivo and in vitro effects of Rhizopus extract on body growth and steroid production in masu salmon, Oncorhynchus masou Brevoort

This study investigated the in vivo and in vitro effects of Rhizopus (filamentous fungus) extract (RU) in masu salmon Oncorhynchus masou Brevoort. Underyearling fish were fed with RU for 16 months. Monthly changes in body growth, gonadal maturation and serum levels of sex steroids were monitored. Gonads were also incubated at 0, 1, 10, 100 and 1000 μg RU mL−1 Leibovitz's L-15 medium for 18 h. The levels of steroids in serum and cultured medium were measured. It was determined that RU-fed immature and mature males, when compared with control groups, showed significantly higher body growth during spring, summer and the spawning period. Similarly, immature RU-fed females showed significantly higher fork length and body weight in autumn, spring and summer. Furthermore, RU-fed males showed significantly higher levels of serum testosterone (T) and 11-ketotestosterone (11-KT) levels in the pre-spawning season, and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) in the spawning season. In vitro RU incubation of gonads showed a dose-dependent and significant increase in T, 11-KT, oestradiol-17β and DHP release in the medium. It appears that the causes of enhanced body growth and increased steroid production herein observed in salmonids are the physiologically active substances that may be present in the mycelium of the fungus.

Clinical observation on treatment of 43 women with polycystic ovary syndrome based on syndrome differentiation

To investigate the therapeutic effect of treatment based on syndrome differentiation and its influence on the serum levels of testosterone and insulin in women with polycystic ovary syndrome (PCOS). Forty-three women, diagnosed with PCOS as well as syndrome of kidney yin deficiency or syndrome of spleen qi deficiency, were enrolled in the study. Twenty-five PCOS women with syndrome of kidney yin deficiency were treated with traditional Chinese herbs for nourishing yin to reduce fire (nourishing yin group), and 18 PCOS women with syndrome of spleen qi deficiency were treated with herbs for invigorating spleen and replenishing qi (replenishing qi group). Body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and the serum levels of insulin and testosterone before and after treatment were detected. Among the 43 cases, 20 cases had high serum testosterone level, in which 13 cases with syndrome of kidney yin deficiency, 7 cases with syndrome of spleen qi deficiency, but the difference had no statistic significance; 17 cases had high serum insulin level, in which 11 cases with syndrome of spleen qi deficiency, 6 cases with syndrome of kidney yin deficiency, the difference had statistic significance (P<0.05). In nourishing yin group, the serum levels of insulin and testosterone declined after treatment (P<0.05), and BMI, WHR and WC showed no significant changes. In replenishing qi group, the serum level of insulin declined after treatment (P<0.01), and BMI, WHR, WC and the serum level of testosterone showed no significant changes. Traditional Chinese herbs for nourishing yin to reduce fire can significantly reduce the serum levels of testosterone and insulin in PCOS women with syndrome of kidney yin deficiency, and herbs for invigorating spleen and replenishing qi can significantly reduce the serum level of insulin in PCOS women with syndrome of spleen qi deficiency.

Does Testosterone Have a Role in Erectile Function?

Purpose Despite the well-established role of testosterone in enhancing libido, its exact contribution to erections in men remains unclear. The main objectives of this review are to clarify the role of testosterone in erectile function and evaluate its therapeutic value in men with erectile dysfunction (ED). Methods Review of the relevant literature (English, French, and Spanish) from 1939 to June 2005 was conducted using data sources from MEDLINE, endocrinology text books, and hand searching of cross-references from original articles and reviews. Clinical trials, animal studies, case reports, reviews, and guidelines of major associations were included. Results Animal and preliminary human studies suggest that testosterone may facilitate erection by acting as vasodilator of the penile arterioles and cavernous sinusoids. Following castration, most, but not all, men had partial or complete loss of erection. Hypogonadism is not a common finding in ED, occurring in about 5% of cases, and in general, there is lack of association between serum testosterone levels, when present in normal or moderately low levels, and erectile function. Most trials using testosterone for treatment of ED in hypogonadal men suffer from methodological problems and report inconsistent results, but overall, suggest that testosterone may be superior to placebo. Erectile function is more likely to improve with testosterone therapy in patients with severe degrees of hypogonadism. Testosterone treatment may ameliorate the response to the phosphodiesterase 5 (PDE5) inhibitors in hypogonadal men and men with low-normal serum testosterone. Repeated measurement of morning serum total testosterone is a fairly accurate and easy method to evaluate androgenecity, but measurement of free or bioavailable testosterone is recommended in conditions that alter the levels of sex-hormone-binding globulin (SHBG), such as in the elderly and in obesity. Conclusions Available data suggest that in most men circulating levels of testosterone, well below the normal range, are essential for normal erection and that higher levels of serum testosterone may not have major impact on erectile function. Screening for hypogonadism in all men with ED is necessary to identify cases of severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment.

Serum Testosterone and the Risk of Prostate Cancer: Potential Implications for Testosterone Therapy

Objective: A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk. Method: Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating. Results: Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.50], 1.16 (95% CI, 0.61-2.20), 2.59 (95% CI, 1.285.25); P trend = 0.03}, which persisted after excluding measures in men <45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% CI, 0.99-3.61); P trend = 0.03]. Compared to men with eugonadal FTI (z0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82). Conclusion: Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point. (Cancer Epidemiol Biomarkers Prev 2005;14(9):2257–60)

A Scleroderma-like Lesion in a Rabbit with Leydig Cell Tumors

A diffuse skin thickening lesion with partial nodular formation in the dorsal lumbar area was found in a 6-year-old male rabbit. Skin biopsy of the nodular lesion revealed a thin epidermis and abundant collagen production in the dermis and subcutis with atrophy of appendages. Findings were mostly consistent with human scleroderma. Three months after the initial examination, enlargement of the left testis was noted, and castration was performed. Histopathological examination demonstrated that both testes were Leydig cell tumors. The high serum testosterone level before castration decreased to within a normal range after castration with partial improvement of the skin lesions. These findings suggest that the Leydig cell tumors in this case caused secretion of excessive testosterone, possibly contributing to the formation of a scleroderma-like lesion.

Th-P15:63 High serum testosterone level is associated with a favorable lipid profile - the tromsø study

Th-P15:63 High serum testosterone level is associated with a favorable lipid profile - the tromsø study

Large Differences in Testosterone Excretion in Korean and Swedish Men Are Strongly Associated with a UDP-Glucuronosyl Transferase 2B17 Polymorphism

The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.

Serum Testosterone and the Risk of Prostate Cancer: Potential Implications for Testosterone Therapy

A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk. Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating. Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.50], 1.16 (95% CI, 0.61-2.20), 2.59 (95% CI, 1.28-5.25); P(trend) = 0.03}, which persisted after excluding measures in men <45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% CI, 0.99-3.61); P(trend) = 0.03]. Compared to men with eugonadal FTI (> or = 0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82). Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point.

Bone turnover markers, anterior pituitary and gonadal hormones, and bone mass evaluation using quantitative computed tomography in ankylosing spondylitis

The objective of this study was to determine bone mineral density (BMD) distribution in ankylosing spondylitis (AS) using quantitative computed tomography (QCT), to study bone turnover and anterior pituitary and gonadal hormonal axis in AS, and to look for correlations between BMD, bone remodeling markers and gonadal and anterior pituitary hormones. Forty-three male consecutive patients with AS were enrolled prospectively [mean (SD) age of 36.4 (11.3) years (range: 17-67) and mean disease duration of 6.8 (5.2) years (range: 0.4-19)]. Spine BMD was measured in all patients by QCT, and the results were compared to 29 male patients undergoing lumbar CT scan for sciatica. Bone turnover and anterior pituitary and gonadal axis were assessed in 29 patients, and the results were compared to 30 male healthy blood donors. The mean (SD) BMD was 127.7 mg/cm(3) (48.9) (range: 8.8-265.7) and 152.1 (25.3) (range: 34.2-190.4) in patients and controls, respectively (p = 0.018). Patients had lower serum levels of osteocalcin and higher levels of serum testosterone, luteinizing hormone (LH), and prolactin than controls with a significant statistical difference. There was a positive significant statistical correlation between BMD and chest expansion, Schober's test, C7-wall distance, and negative significant statistical correlation with age, disease duration, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), and serum prolactin. No correlation was observed between bone turnover parameters and AS symptomatic and structural severity indexes. BMD is lower with increasing age and late and severe disease. Decreased bone formation with normal resorption and increased levels of serum prolactin may be involved in its pathophysiology.

Human impulsive aggression: a sleep research perspective

Impulsive aggression is commonly associated with personality disorders, in particular antisocial and borderline personality disorders as well as with conduct disorder and intermittent explosive disorder. The relationship between impulsive aggression and testosterone is well established in many studies. One of the aims of this study was to characterize the relationship between earlier-mentioned different categorical psychiatric diagnosis describing human impulsive aggression and sleep using polysomnography and spectral power analysis. Another aim was to study the relationship between serum testosterone and sleep in persons with severe aggressive behaviour. Subjects for the study were 16 males charged with highly violent offences and ordered for a pretrial forensic psychiatric examination. The antisocials with borderline personality disorder comorbidity had significantly more awakenings and lower sleep efficiency compared with the subjects with only antisocial personality disorder. The subjects with severe conduct disorder in childhood anamnesis had higher amount of S4 sleep and higher relative theta and delta power in this sleep stage compared with males with only mild or moderate conduct disorder. The same kind of sleep architecture was associated with intermittent explosive disorder. In subgroups with higher serum testosterone levels also the amount of S4 sleep and the relative theta and delta power in this sleep stage were increased. The study gives further support to the growing evidence of brain dysfunction predisposing to severe aggressive behaviour and strengthens the view that there are different subpopulations of individuals with antisocial personality varying in impulsiveness. The differences in impulsiveness are reflected in sleep architecture as well.

Overexpression of human chorionic gonadotropin causes multiple reproductive defects in transgenic mice.

Human CG is a pregnancy marker secreted by the placenta, and it utilizes the same receptors as does LH. Human CG is a heterodimer, and its subunits are expressed in tissues other than placenta. Similarly, LH/hCG receptors are also expressed in multiple tissues; however, the physiological significance of this expression is unknown. Free hCGbeta is efficiently secreted in vitro in transfected cells and is highly expressed in many human cancers; however, the biological effects of free hCGbeta in vivo are unknown. To study in vivo consequences of elevated levels of free hCGbeta and hCG dimer in both male and female reproductive physiology, we used mouse metallothionein 1 promoter to generate multiple lines of transgenic mice that overexpressed either one or both subunits of hCG. Although mice expressing the glycoprotein hormone alpha subunit are normal and fertile, both male and female transgenic mice overexpressing only the hormone-specific hCGbeta subunit are infertile. The hCGbeta subunit-expressing transgenic female mice progressively develop cystic ovaries, whereas the male transgenic mice are infertile but otherwise are not phenotypically discernible. In contrast, both the male and female transgenic mice coexpressing high levels of the hCG subunits (i.e., the hCG dimer) demonstrate multiple reproductive defects. The male transgenic mice have Leydig cell hyperplasia, very high levels of serum testosterone, reduced testis size, and dramatically enlarged seminal vesicles and are infertile and display overly aggressive behavior when caged with females. The female transgenic mice are also infertile, have elevated levels of serum estradiol, and progressively develop hemorrhagic and cystic ovaries with thecal layer enlargement and stromal cell proliferation and degenerating kidneys. These results suggest that the in vivo biological effects of ectopically expressed free hCGbeta subunit are distinct from those of the hCG dimer and are gender specific. These transgenic mice are useful models for studying the biology of free hCGbeta subunit, for further analyzing the gain of function effects of hCG during early Leydig cell development, and for studying the roles of hCG in ovarian and kidney pathophysiology and function.

Relationship of the hormone-sensitive lipase-mediated modulation of cholesterol metabolism in individual compartments of the testis to serum pituitary hormone and testosterone concentrations in a seasonal breeder, the mink (Mustela vison).

The role of cholesterol differs in the two compartments of the testis. In the interstitial tissue, cholesterol is necessary for the synthesis of testosterone, whereas in the seminiferous tubules, membrane cholesterol content in developing germ cells will influence the gametes' fertility. Here we evaluate the hormone-sensitive lipase (HSL) modulation of the cholesterol metabolism in each compartment of the testis. Two HSL immunoreactive bands of 104- and 108-kDa were detected in Western blots performed with polyclonal anti-human HSL antibodies in the interstitial tissue (ITf)- and seminiferous tubule (STf)-enriched fractions generated from testes harvested at 30-day intervals during puberty and, in the adult mink, during the annual seasonal reproductive cycle. Epididymal spermatozoa expressed a 104-kDa HSL isoform, and HSL was active in these cells. Immunolabeling localized HSL to interstitial macrophages; Sertoli cells, where its distribution was stage specific; spermatids; and the equatorial segment of spermatozoa. Total HSL protein levels, specific enzymatic activity, and free cholesterol (FC):esterified cholesterol (EC) ratios varied concomitantly in STf and ITf and reached maximal values in the adult during the period of maximal spermatogenic activity. In STf, HSL-specific activity correlated with FC:EC ratios but not with triglyceride levels. In STf, high HSL-specific activity occurred concomitantly with high FSH serum levels. In ITf, HSL-specific activity was high during periods of low serum prolactin levels and high serum testosterone levels. The results suggest that 1) modulation of cholesterol metabolism in individual testicular compartments may be regulated by HSL isoforms expressed by distinct cells; 2) interstitial macrophages may be part of a system involved in the synthesis of steroid hormones and in the recycling of sterols in the interstitium, whereas in the tubules, recycling could be ensured by Sertoli cells; 3) there is distinctive substrate preference for testicular HSL; and 4) HSL may be the only cholesterol esterase in this location.