Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer

Androgens are considered to play a substantial role in pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. The importance of determination of androgen levels in tissue and serum for cancer progression and prognosis has been poorly understood. The aim of study was to find out hormonal differences in both diseases, their correlations between intraprostatic and serum levels and predicted value of their investigation. Testosterone, dihydrotestosterone, androstenedione and also epitestosterone were determined in prostate tissue from 57 patients who underwent transvesical prostatectomy for BPH and 121 patients after radical prostatectomy for prostate cancer. In 75 subjects with cancer and 51 with BPH the serum samples were analyzed for testosterone, dihydrotestosterone and SHBG. Significantly higher intraprostatic androgen concentrations, i.e. 8.85+/-6.77 versus 6.44+/-6.43 pmol/g, p<0.01 for dihydrotestosterone, and 4.61+/-7.02 versus 3.44+/-4.53 pmol/g, p<0.05 for testosterone, respectively, were found in patients with prostate cancer than in BPH. Higher levels in cancer tissue were found also for epitestosterone. However, no differences were found in serum levels. Highly significant correlations occurred between all pairs of intraprostatic androgens and also epitestosterone as well as between serum testosterone and dihydrotestosterone (p<0.001) in both BPH and cancer groups. Correlation was not found between corresponding tissue and serum testosterone and dihydrotestosterone, either in benign or cancer samples. The results point to importance of intraprostatic hormone levels for evaluation of androgen status of patients, contrasting to a low value of serum hormone measurement.     

A safer method for studying hormone metabolism in an Asian elephant (Elephas maximus): accelerator mass spectrometry

Noninvasive hormone assays provide a way to determine an animal's health or reproductive status without the need for physical or chemical restraint, both of which create unnecessary stress for the animal, and can potentially alter the hormones being measured. Because hormone metabolism is highly species‐specific, each assay must be validated for use in the species of interest. Validation of noninvasive steroid hormone assays has traditionally required the administration of relatively high doses of radiolabelled compounds (100 µCi or more of ¹⁴C labeled hormone) to permit subsequent detection of the excreted metabolites in the urine and feces. Accelerator mass spectrometry (AMS) is sensitive to extremely low levels of rare isotopes such as ¹⁴C, and provides a way to validate hormone assays using much lower levels of radioactivity than those traditionally employed. A captive Asian bull elephant was given 1 µCi of ¹⁴C‐testosterone intravenously, and an opportunistic urine sample was collected 2 hr after the injection. The sample was separated by HPLC and the ¹⁴C in the fractions was detected by AMS to characterize the metabolites present in the urine. A previously established HPLC protocol was used, which permitted the identification of fractions into which testosterone sulfate, testosterone glucuronide, and the parent compound testosterone elute. Results from this study indicate that the majority of testosterone excreted in the urine of the Asian bull elephant is in the form of testosterone sulfate. A small amount of testosterone glucuronide is also excreted, but there is no parent compound present in the urine at all. These results underscore the need for enzymatic hydrolysis to prepare urine samples for hormone assay measurement. Furthermore, they highlight the importance of proper hormone assay validation in order to ensure accurate measurement of the desired hormone. Although this study demonstrated the utility of AMS for safer validation of noninvasive hormone assays in nondomestic species, this methodology could also be applied to studies of nutrient metabolism and drug pharmakokinetics, both areas in great need of further study in wildlife species. Zoo Biol 29:760–766, 2010. © 2010 Wiley‐Liss, Inc.     

Maternally derived yolk hormones vary in follicles of the painted turtle,Chrysemys picta

The transfer of hormones from a female to her offspring is known to occur in egg laying vertebrates, and the potential for these early, maternally derived hormones to influence sex determination in reptiles with temperature-dependent sex determination is intriguing. In the present study, we examine variation in the concentrations of progesterone, testosterone, and estradiol among three follicle size classes within a female painted turtle (Chrysemys picta) and among females across four periods that span the pre- to post-nesting season. Females were collected, and both follicles and shelled eggs (when present) were harvested for hormone analysis. Progesterone levels did not vary seasonally. However, the concentration of progesterone did vary among and within follicle classes, and was primarily dependent upon ovulatory state: Recently ovulated follicles (as yolks within shelled eggs) contained significantly more progesterone than unovulated follicles. Concentrations of testosterone were low and did not vary either among size classes or across the season. Estradiol levels decreased with increasing follicle size and were higher later in the nesting season. Thus, hormone concentrations varied among follicle sizes and states but in patterns that differed among hormones. This variation has the potential to influence sex determination.     

Sex steroid hormones and cognitive functioning in healthy, older men

The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men. Regression analyses revealed significant curvilinear associations between working memory function and both free and bioavailable testosterone levels, suggesting that an optimal hormone level may exist for maximal performance on tasks of executive/frontal lobe functioning. However, no other relationships were evident between either estradiol or testosterone levels and any of the other cognitive functions evaluated. Hormone assays performed at the end of the study revealed that a considerable portion of the healthy elderly men in our sample met criteria for hypogonadism and suggests that their low hormone levels may have mitigated against discovering other significant hormone-cognition relationships.     

睾酮对去睾丸家兔骨密度及血清钙磷的影响

目的:观察去睾丸和睾酮补充对雄兔骨密度和血清钙、镁、磷的影响.方法:周龄相同的雄性新西兰白兔随机分成对照组、去睾丸组和睾酮补充组(去睾丸后肌注十一酸睾酮).同等条件下饲养20周后测量各组兔全身骨密度、腰椎骨密度、股骨颈骨密度,并检测血清总睾酮(TT)、雌二醇(E2),脱氢表雄酮(DHEA)水平以及血清钙(Ca2 )、游离钙([Ca2 ]i)镁(Mg2 )、磷(P)和碱性磷酸酶(AKP)浓度.结果:去睾丸组血清TT水平明显下降(P<0.01),睾酮补充组血清TT水平升高接近对照组(P>0.05).去睾丸组血清E2和E2/TT比明显高于对照组(P<0.01),睾酮补充组血清E2和E2/TT下降,接近对照组水平(P均>0.05).与对照组相比,去睾丸组血清Ca2 、[Ca2 ]i、Mg2 以及AKP浓度明显升高(P均<0.01),睾酮补充组血清Ca2 、[Ca2 ]i、Mg2 以及AKP浓度较去睾丸组低,接近对照组水平(P>0.05).股骨颈骨密度在去睾丸组明显低于对照组和睾酮补充组(P<0.01),而后两组无差别(P>0.05).结论:去睾丸后雄兔血清TT明显下降,E2和E2/TT比以及Ca2 、[Ca2 ]i、Mg2 和AKP浓度明显升高,骨密度显著下降,睾酮补充使上述异常明显改善.     

Neither testosterone levels nor aggression decrease when the male Mongolian gerbil (Meriones unguiculatus) displays paternal behavior

The first studies that correlated mammalian paternal behavior and testosterone levels indicated that the concentration of this steroid hormone decreases when males exhibit paternal care. However, recent studies have also shown that testosterone levels do not decrease when males display paternal behavior. In this study, we measured testosterone levels in plasma throughout the reproductive cycle of the Mongolian gerbil. Testosterone concentrations were correlated with paternal care as well as aggression. We also examined whether there is a trade-off between paternal behavior and aggression in this mammal. Our results show that Mongolian gerbil testosterone levels do not decrease when the males give paternal care. Likewise, male Mongolian gerbils exhibit high levels of aggression while displaying paternal behavior, indicating that there is no trade-off between aggression and paternal behavior. More studies are needed to determine whether testosterone is involved in the regulation of paternal behavior in this rodent.     

Gonadal function in male mountain bikers

Some studies reported testicular disorders associated with biking in mountain cyclists, which include injuries, erectile dysfunction, and higher scrotal temperatures. But none of these studies evaluated gonadal function. Therefore, the aim of this study was to evaluate gonadal function in male mountain bikers. Twenty-two male professional mountain bikers and 30 healthy noncyclist controls were included in the study. The mean age and body mass index were similar in both groups. Fasting blood samples for the measurement of the levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were obtained from all study participants before any physical activity. In addition, because insulin sensitivity and leptin modulate gonadal function, the concentrations of insulin, glucose, and leptin were also measured in the same samples. Calculated free testosterone (cFT) and bioavailable testosterone (bioT) were calculated from SHBG and TT. Basal hormonal levels including insulin, leptin, LH, FSH, SHBG, TT, glucose, and homeostasis model assessment scores were similar between the groups. However, bioT and cFT levels were significantly lower (p ≤ 0.05) in the mountain bikers than those in the controls. Despite the lower mean testosterone levels in the study group, the levels of LH and FSH were similar to controls. Insulin and leptin do not contribute to lower testosterone levels. In conclusion, male mountain bikers have lower testosterone concentrations compared to controls. This alteration cannot solely be explained by testicular dysfunction. The etiology of lower testosterone levels in cyclists appears to be complex and requires further research. The influence of such a decline on the athlete's performance, quality of life, and muscle strength is not known as yet.     

Optimizing Diagnostic Accuracy and Treatment Decisions in Men With Testosterone Deficiency

ObjectiveThis narrative review offers a guideline-based approach for optimizing diagnostic evaluation and treatment decision making in men being evaluated for testosterone deficiency.MethodsA narrative review.ResultsTestosterone deficiency is a clinical syndrome that results from the inability of the testes to produce normal amounts of testosterone and is characterized by a constellation of symptoms and signs associated with consistently low testosterone concentrations. The diagnosis of testosterone deficiency is made by the ascertainment of symptoms and signs; the measurement of total and, if indicated, free testosterone levels in early-morning fasting samples on ≥2 days; the measurement of luteinizing hormone and follicular-stimulating hormone levels to distinguish primary from secondary hypogonadism; and an additional evaluation to ascertain the cause of testosterone deficiency. Nonspecificity of symptoms and signs, variations in testosterone levels over time, inaccuracy in the measurement of total and free testosterone levels, variations in binding protein concentrations, and suboptimal reference ranges contribute to diagnostic inaccuracy. Testosterone treatment is indicated for men with symptomatic testosterone deficiency. Testosterone treatment should be avoided in men with prostate or breast cancer, erythrocytosis, thrombophilia, increased risk of prostate cancer or severe lower urinary tract symptoms without prior urologic evaluation, a recent major adverse cardiovascular event, uncontrolled heart failure, or severe untreated sleep apnea. Testosterone replacement therapy should be accompanied by a standardized monitoring plan.ConclusionA shared decision of the patient and physician to treat should be guided by the consideration of the burden of symptoms, potential benefits and risks, patient’s values, and the cost and burden of long-term treatment and monitoring.     

Cortisol levels are positively associated with pup-feeding rates in male meerkats

In societies of cooperative vertebrates, individual differences in contributions to offspring care are commonly substantial. Recent attempts to explain the causes of this variation have focused on correlations between contributions to care and the protein hormone prolactin, or the steroid hormone testosterone. However, such studies have seldom considered the importance of other hormones or controlled for non-hormonal factors that are correlative with both individual hormone levels and contributions to care. Using multivariate statistics, we show that hormone levels explain significant variation in contributions to pup-feeding by male meerkats, even after controlling for non-hormonal effects. However, long-term contributions to pup provisioning were significantly and positively correlated with plasma levels of cortisol rather than prolactin, while plasma levels of testosterone were not related to individual patterns of pup-feeding. Furthermore, a playback experiment that used pup begging calls to increase the feeding rates of male helpers gave rise to parallel increases in plasma cortisol levels, whilst prolactin and testosterone levels remained unchanged. Our findings confirm that hormones can explain significant amounts of variation in contributions to offspring feeding, and that cortisol, not prolactin, is the hormone most strongly associated with pup-feeding in cooperative male meerkats.     

Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome

Testosterone is a potent regulator of lipolysis by influencing catecholamine signal transduction in fat cells. Major species differences exist as regards the testosterone effect. In rodents testosterone increases beta-adrenergic receptor mediated signals to lipolysis at multiple steps in the lipolytic cascade. The sex hormone also increases alpha2-adrenoceptor antilipolytic signalling in hamster which unlike rat express this receptor in their fat cells. In humans the region of adipose tissue is critical. Visceral fat cell lipolysis is not responsive to testosterone but this sex hormone decreases catecholamine-induced lipolysis in subcutaneous fat cells due to inhibition of the expression of beta2-adrenoceptors and hormone sensitive lipase. In polycystic ovarian syndrome (PCOS), which is characterized as a hyperandrogenic state, the lipolytic effect of catecholamine is decreased in subcutaneous adipocytes due to low content of beta2-adrenoceptors and hormone sensitive lipase. It is possible that the increased testosterone levels are responsible for these abnormalities in catecholamine signal transduction in subcutaneous fat cells of PCOS women. However, in visceral fat cells of PCOS women catecholamine-induced lipolysis is enhanced which cannot be explained by testosterone.     

Sex hormone profiles of premenarcheal athletes

Female gymnasts have a delayed onset and probably retarded progression of puberty. The aim of this study was to test the hypothesis that the delay in onset of puberty in gymnasts as compared to girl swimmers is modulated by a lower estrone level due to a smaller amount of body fat. The sex-hormone and gonadotropin levels of 46 gymnasts and 37 girl swimmers of the same biological maturation (breast development: M = 1 or M = 2) were studied. In each subject the following hormones were measured in plasma: estrone, 17-beta-estradiol, DHEAS, testosterone, androstenedione, LH, and FSH. In prepubertal children (M = 1) the levels of estrone, testosterone, and androstenedione were lower in the gymnastic group as compared to the swimming group. In the early pubertal (M = 2) gymnastic and swimming groups these hormone levels were no longer different. The other hormone levels were not significantly different in either the prepubertal groups or the early pubertal ones. Within the total prepubertal group there is a clear relationship between the estrone levels and the levels of testosterone and androstenedione, but not between estrone and 17-beta-estradiol, nor between the calculated fat mass and any of the hormone levels. It appears that the androstenedione and testosterone levels are responsible for the difference in estrone level, rather than the amount of body fat.     

Selective contributions of the medial preoptic nucleus to testosterone-dependant regulation of the paraventricular nucleus of the hypothalamus and the HPA axis

Previous data have consistently demonstrated an inhibitory effect of androgens on stress-induced hypothalamic-pituitary-adrenal (HPA) responses. Several brain regions may influence androgen-mediated inhibition of the HPA axis, including the medial preoptic area. To test the role of the medial preoptic nucleus (MPN) specifically, we examined in high- and low-testosterone-replaced gonadectomized rats bearing discrete bilateral lesions of the MPN basal and stress-induced indexes of HPA function, and the relative levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the amygdala. High testosterone replacement decreased plasma adrenocorticotropin hormone (ACTH) and paraventricular nucleus (PVN) Fos responses to restraint exposure in sham- but not in MPN-lesioned animals. AVP-, but not CRH-immunoreactivity staining in the external zone of the median eminence was increased by testosterone in sham animals, and MPN lesions blocked this increment in AVP. A similar interaction between MPN lesions and testosterone occurred on AVP mRNA levels in the medial nucleus of the amygdala. These findings support an involvement of MPN projections in mediating the AVP response to testosterone in both the medial parvocellular PVN and medial amygdala. We conclude that the MPN forms part of an integral circuit that mediates the central effects of gonadal status on neuroendocrine and central stress responses.     

Concentration of unconjugated adrenogenic hormones and their precursors in normal and polycystic ovaries.

Dehydroepiandrosterone, androstenedione, testosterone, pregnenolone and progesterone concentration was determined by our sensitive gas-liquid chromatographic method in ovarian tissues obtained from surgery of patients without hirsutism and with Stein-Leventhal syndrome. The steroids, except testosterone, were detectable in all ovaries studied. Dehydroepiandrosterone and androstenedione, regarded as preandrogens, were present in an increased amount in almost all patients with polycycstic ovaries. Gas chromatographic evidence was obtained for the presence of testosterone in two of the cases. The delta4/3betaOH ratio reflecting 3beta-hydroxysteroid dehydrogenase activity was decreased only in same patients with the Stein-Leventhal syndrome suggesting that the impaired function of this enzyme is not an obligatory feature of polycystic ovaries. Concentration of pregnenolone and progesterone measured in a part of cases varied in a great range although the determination was caried out before luteal phase. Simultaneous determination of hormones in both ovarian tissues revealed an active and an inactive period of the gland in the given time, since a great difference of hormone concentration in bilateral ovarian tissues were observed. A comparison of hormone content in ovaries and the urinary excretion of metabolites showed poor correlation between the two parameters of hormone production.     

Faecal sexual steroids in sex typing and endocrine status of great bustards

Faecal sexual steroids have been used in field studies evaluating the relationships between gender and the multiple factors influencing endocrine status of individuals. The determination of faecal steroids has been also proposed as an alternative, non-invasive sexing method when other methods were deemed impractical or risky for the health of birds. In this study, we quantified sexual steroid hormones in faeces of the great bustard (Otis tarda), a large and sexually dimorphic polyginic bird species that it is threatened and subjected to intense wildlife management. We evaluated differences between captivity and wild conditions, flocks and sexes, and used faecal steroids to develop sex determination procedures. We found similar steroid levels in captive and wild bustards, no differences between unisexual wild flocks and clear between-sexes differences in testosterone but not estradiol. Faecal steroids accurately discriminated gender in both captive and wild known-sex great bustards. Total testosterone concentration was always higher than estradiol concentration in faecal samples from males, but estradiol was not always higher than testosterone in females. Faecal steroids failed to reveal the presence of young males in female flocks during winter, despite faecal testosterone levels increased with age in a small sample of captive males. Our results show that faecal steroid measurement for both sexing and characterizing the endocrine status of great bustards is feasible, and therefore it should be valuable in wildlife management, especially in combination with additional information obtained from faeces as diet.     

Common and specific effects of the two major forms of prolactin in the rat testis

Prolactin (PRL) has both stimulatory and inhibitory effects on testicular function, a finding we hypothesized may be related in some part to the form of the hormone present or administered. In the analysis of the pituitary secretion profiles of early pubescent vs. mature male rats, we found PRL released from early pubescent pituitaries had about twice the degree of phosphorylation. Treatment of mature males with either unmodified PRL (U-PRL) or phosphorylated PRL (via the molecular mimic S179D PRL) for a period of 4 wk (circulating level of approximately 50 ng/ml) showed serum testosterone decreased by approximately 35% only by treatment with the phospho-mimic S179D PRL. Given the specificity of this effect, it was initially surprising that both forms of PRL decreased testicular expression of 3beta-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Both forms also increased expression of the luteinizing hormone receptor, but only S179D PRL increased the ratio of short to long PRL receptors. Endogenous PRL and luteinizing hormone levels were unchanged in all groups in this time frame, suggesting that effects on steroidogenic gene expression were directly on the testis. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling analysis combined with staining for 3beta-hydroxysteroid dehydrogenase and morphometric analysis showed that S179D PRL, but not U-PRL, increased apoptosis of Leydig cells, a finding supported by increased staining for Fas and Fas ligand in the testicular interstitium, providing an explanation for the specific effect on testosterone. S179D PRL, but not U-PRL, also increased apoptosis of primary spermatogonia, and U-PRL, but not S179D PRL, decreased apoptosis of elongating spermatids. Thus, in mature males, hyperprolactinemic levels of both forms of PRL have common effects on steroidogenic proteins, but specific effects on the apoptosis of Leydig and germ cells.     

Reproductive hormone profiles in captive male orangutans: Implications for understanding developmental arrest

For many years researchers have described some male orangutans as “subadult.” These males are of adolescent to adult age and are reproductive, but have little to no secondary sexual trait development. Until now the only endocrine study of this arrest of secondary sexual trait development was performed by Kingsley (1982, 1988). She found that “subadult” or arrested males have lower testosterone levels than similar age developing adolescents or adult males. In this study, urine samples were collected over a two-year period from 23 captive male orangutans in order to more fully define male endocrine profiles. Three study males were juveniles, seven were arrested adolescents, six were developing adolescents, and seven were mature adults. Morning samples were analyzed by radioimmunoassay for levels of testicular steroids and gonadotropins and group hormone profiles were compared by analysis of variance. Results illustrate that arrested adolescent orangutans have significantly lower testosterone and dihydrotestosterone (DHT) levels than developing adolescents, but significantly higher levels than juveniles. Luteinizing hormone (LH) levels also differed between arrested and developing adolescents, with arrested males having lower levels. However, follicle stimulating hormone (FSH) levels were similar in both morphs of adolescent male. The overall hormone profiles for arrested and developing adolescent male orangutans suggest that arrested males lack levels of LH, testosterone, and DHT necessary for development of secondary sexual traits. However, they have sufficient testicular steroids, LH, and FSH to fully develop primary sexual function and fertility. These endocrine data help define alternative developmental pathways in male orangutans. The authors discuss the relationship between these developmental pathways and male orangutan reproductive strategies, and hypothesize about their prepubertal socioendocrine determination. Am J Phys Anthropol 109:19–32, 1999. © 1999 Wiley-Liss, Inc.     

Seasonality of semen production and plasma luteinizing hormone,testosterone and prolactin levels in Romney,Merino and polled dorset rams

An attempt was made to define the seasonality of reproduction in rams in the southern hemisphere by repeated measurement of semen characteristics and of plasma luteinizing hormone (LH), testosterone and prolactin concentrations. These parameters were studied for 16 months in Romney rams on pasture, with Merino and Polled Dorset rams included for comparison.Semen from all three breeds showed regular seasonal changes in ejaculate volumes, with peak values being recorded during March. A similar autumnal peak of seminal fructose levels was noted for ejaculates from Romney and Merino rams, but not for those from Polled Dorsets. Most of the other semen parameters measured showed little tendency for seasonal variations. However, a change in semen collection technique, from predominantly artificial vagina to entirely electroejaculation, may have masked some seasonal changes.Plasma hormone levels also varied in a regular manner, with peak levels occurring in summer and autumn: highest levels for prolactin were recorded in November–March, for LH in December–February and for testosterone in January–March. An exception to this pattern was recorded from the Merino rams, for which there was no definite peak of LH secretion.It is suggested that these seasonal changes resulted primarily from changes in daily photoperiod.     

Gonadal function in trisomy 21

Endocrinologic evaluation of 39 patients with trisomy 2 and associated hypogonadism demonstrated elevations of follicle-stimulating hormone and luteinizing hormone; consequently, it can be concluded that both germinal and Leydig cell function are affected. A negative correlation between testicular size and plasma follicle-stimulating hormone was documented. Plasma testosterone levels were found to be normal in male patients as were estradiol levels in female patients with trisomy 21. On the basis of these findings, the simplest and most practical diagnostic approach to evaluate germinal cell function appears to be a single plasma follicle-stimulating hormone determination supplemented by an accurate measurement of testicular volume in males.     

Plasma steroid hormones in relation to behavioral sex role reversal in the spotted sandpiper, Actitis macularia

Plasma samples collected from spotted sandpipers during the reproductive season were analyzed for testosterone, dihydrotestosterone (DHT), estradiol-17 beta and progesterone. Prior to incubation, plasma testosterone and DHT levels were significantly greater in males than in females. Estradiol levels of paired females were significantly greater than those of paired males. Testosterone and DHT levels of unpaired resident and paired males were significantly greater than those of incubating and brooding males. A 25-fold decline in testosterone occurred in males from the 1- or 2-egg stage to the 3-egg stage, when incubation is initiated. In females, testosterone values were low in unpaired, brooding, and transient birds. Paired females had levels 7-fold greater than unpaired birds. In both sexes, there was a strong correlation between testosterone and DHT levels. Prolactin values were negatively correlated with testosterone and DHT in males. These results indicate that the high level of intrasexual competition for mates among female spotted sandpipers is not based upon a total reversal of the normal male/female levels of androgens and estradiol. Territoriality and intense competition for mates in females may be based upon enhanced receptivity of neural centers to moderate hormone levels. Relative changes in testosterone between unpaired and paired females indicates that this hormone may play a role in mate acquisition and territoriality of these sex role-reversed females.     

Pretranslational regulation of sex-dependent testosterone hydroxylases by growth hormone in mouse liver

The effects of growth hormone on the expression of sex-dependent testosterone 16 alpha- and 15 alpha-hydroxylases were studied in growth hormone-deficient Little (lit/lit) mice at the activity as well as at the mRNA levels. The male isozyme of testosterone 16 alpha-hydroxylase ("C"-P-450(16)alpha) was repressed in the liver of male lit/lit mice, and the injection of bovine growth hormone resulted in an increase of the isozyme at both activity and mRNA levels to those seen in control lit/+ male mice. On the other hand, the female isozymes of testosterone 16 alpha- ("I"-P-450(16)alpha) and 15 alpha-hydroxylase (P-450(15)alpha) were increased in livers of both male and female lit/lit mice. The increased I-P-450(16)alpha and P-450(15)alpha in lit/lit mice were suppressed by growth hormone but only when it was injected once every 12 h. Thus, the results indicate that growth hormone acts as a masculinizing factor for testosterone hydroxylase activity by activating and inhibiting the expression of male and female isozymes of testosterone hydroxylases in mice, respectively. When growth hormone was infused to simulate a continuous secretion pattern, it showed no significant effect on the expression of hydroxylases in lit/lit mice, suggesting that growth hormone may not be a feminizing factor for testosterone hydroxylase activity in female mice. The changes of specific hydroxylase activities modulated by growth hormone in the mice correlated well with those amounts of hydroxylase mRNAs. The action of exogenous growth hormone to regulate the hydroxylases was so slow that it took 2 days to show a significant effect.