Successful pregnancy in a woman with ovarian failure associated with mutation in the beta-subunit of luteinizing hormone.

BACKGROUND: We report a successful pregnancy in a woman with severe ovarian dysfunction and infertility associated with a variant beta-subunit of luteinizing hormone (LH). METHOD/OUTCOME: A 35-year-old woman consulted our unit for infertility. Laparoscopy and ultrasonography showed obstruction of the right tube and ovulation from the right ovary only. Human menopausal gonadotrophin (hMG) therapy was used for six subsequent cycles, but did not result in conception. Subsequently, marked elevation of follicle-stimulating hormone (FSH) and testosterone, together with polycystic ovary (PCO) were noted. The patient failed to respond to ovarian stimulation by hMG. Severe ovarian dysfunction such as premature ovarian failure (POF) was strongly suspected. Sequence analysis of the LH beta-subunit gene indicated heterozygosity for point mutations Trp(8) to Arg(8) and Ile(15) to Thr(15) in the coding sequence. LH hypersecretion resembling that seen in PCO syndrome was observed. Induction of ovulation by hMG was successful in the first cycle in which the basal LH and FSH were well controlled with gonadotrophin-releasing hormone analog following estrogen-progesterone replacement. She conceived and delivered a healthy male infant at term. CONCLUSION: Clinicians should be clinically aware of patients with immunologically anomalous LH variant who might be at risk of developing ovarian failure within a relatively short time span. Pertinent treatment should be applied without delay in such cases.     

Plasma and pituitary concentrations of gonadotropins (FSH and LH) in minke whales (Balaenoptera acutorostrata) during the feeding season

This study investigated plasma and pituitary concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and steroid hormones (progesterone: P4, testosterone:T, estradiol-17beta: E2) by enzyme-immunoassay (EIA) in minke whales (Balaenoptera acutorostrata) captured during the feeding season (December to March) in the Antarctic Ocean. Plasma FSH and LH levels in female minke whales were higher (P <0.05) than in male whales. Although the pituitary weight was not significantly different between male and female whales, pituitary FSH and LH levels were higher in females than in males (P<0.01) and mature whales than immature whales (P<0.05). Plasma levels of FSH, T and E2 were not significantly different between immature and mature male whales, but plasma LH and pituitary FSH and LH levels were higher (P<0.05) in mature than in immature whales. In both immature and mature whales regardless of gender, pituitary FSH and LH levels were correlated significantly (r=0.69: P<0.01). In mature male whales, plasma T and E2 levels (r=0.60: P<0.01), and testis weight and plasma T levels (r=0.46: P <0.05) were correlated. In immature female whales, plasma FSH and LH levels were highly correlated (r=0.68: P<0.001), but were not for mature female whales. The results show that gender and maturity influence gonadal and pituitary function of minke whales during the feeding season.     

Influence of gonadal hormones on endocrine activity of gonadotroph cells in the adenohypophysis of male lambs during the postnatal transition to puberty

Using histomorphological and functional criteria we describe the feedback mechanisms which could play a role in the regulation of the gonadotrophic axis during the postnatal transition to puberty in male lambs. The working hypothesis was that the testicular factors change the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by influencing the synthesis rate and storage of LH and FSH in adenohypophyseal gonadotroph cells of weanling and weaned pubertal lambs. The examination was made in (i) 9-week-old infantiles, suckling lambs undergoing weaning, testis-intact (TEI) and orchidectomised (ORCHX) at the 6th week of age, and (ii) 16-week-old pubertal lambs TEI and ORCHX at the 12th week of age (n=5 per group). Changes in gonadotrophs were assayed with hybridohistochemistry, immunohistochemistry and radioimmunoassay. The percentage of the adenohypophyseal area (PA) occupied by cells containing LHβ-mRNA and FSHβ-mRNA and peripheral levels of both gonadotrophins were lower (P<0.01) in the 16-week-old TEI lambs in comparison with the 9-week-old ones. The PA occupied by cells immunoreactive for LHβ was lower (P<0.01), whereas in the case of FSH was greater (P<0.001) in the 16-week-old lambs. After orchidectomy the PA occupied by gonadotrophs stained for LHβ-mRNA was greater (P<0.01) in 16-week-old lambs. The PA occupied by LHβ-labelled cells was lower (P<0.05) in the 9-week-old ORCHX lambs, whereas in 16-week-old ones was higher (P<0.05) in comparison with the TEI lambs. The circulating LH was greater (P<0.01) in the ORCHX 9- and 16-week-old lambs compared to the TEI ones. The PA occupied by cells containing FSHβ-mRNA and the plasma FSH concentration were greater (P<0.001) after orchidectomy in lambs from both age stages. The PA occupied by FSHβ-labelled cells was greater (P<0.01) in the 9-week-old ORCHX lambs, whereas in 16-week-old ones was lower (P<0.05) compared to the lambs from TEI groups. In conclusion, in infantile lambs testicular factors may play inhibitory role in regulating FSH synthesis rate, storage and release in contrast to the stimulatory role in regulating LH storage reflected by the inhibitory role in regulating LH release. In lambs at the beginning of puberty, testicular factors may play inhibitory role in regulating LH synthesis rate, storage and release in contrast to the stimulatory role in regulating FSH storage reflected by the inhibitory role in regulating FSH synthesis rate and release. The effects of testicular hormones on the gonadotrophin storage, i.e. releasable pools in adenohypophyseal cells, are specific for both LH and FSH in lambs during the postnatal transition to puberty. Thus, the initiation of puberty in male sheep is a function of change of the inhibitory role of gonadal factors in regulating FSH storage to the stimulatory one and the stimulatory role of gonadal factors in regulating LH storage to the inhibitory one.     

Altered kinetics of pituitary response to gonadotropin-releasing hormone in women with variant luteinizing hormone: correlation with ovulatory disorders

OBJECTIVE: The LH response of pituitary gland to gonadotropin-releasing hormone (GnRH) stimulation is not well defined in patients with mutant beta-subunit (Trp(8) to Arg(8) and Ile(15) to Thr(15)). Here we compared the relative activities and dynamics of LH secretion in patients with wild-type and variant LH following injection of GnRH. METHODS: A GnRH stimulation test was performed in 33 patients with ovulatory disorders (patient group) and 29 women with normal ovulatory cycles (control group) heterozygous for the variant LHbeta allele. Blood samples were obtained up to 120 min after GnRH injection. Serum LH response was determined by comparing the results of LH immunoassays using a monoclonal antibody that recognizes wild-type LH only with those of another assay using a polyclonal antibody that recognizes equally both variant and wild-type LH (total LH). The ratio of variant LH to total LH (LH ratio) was used to determine the serum LH status. RESULTS: The LH ratio in the control group showed the peak 15 min after GnRH injection, while that in the patient group showed the peaks 30-60 min after injection. The LH ratio in the patient group at 120 min after injection was significantly lower than that in the control group. The percent increases in LH ratio in both groups showed the peak 15 min after injection. The patient group had significantly lower changes of LH ratio at 15, 60, 90 and 120 min after GnRH injection compared with that in the control group. CONCLUSION: Differences in circulatory kinetics of the two types of LH may explain the differences in LH function between patients with ovulatory disorders and women with normal ovulatory cycles.     

LH responses to single doses of exogenous GnRH by social Mashona mole-rats: a continuum of socially induced infertility in the family Bathyergidae.

The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair. The non-reproductive male and female colony members are restrained from sexual activity by being familiar and related to one another and the reproductive animals. Circulating basal concentrations of luteinizing hormone (LH) as well as LH levels measured in response to a single exogenous gonadotropin releasing hormone (GnRH) challenge are not significantly different between the reproductive and non-reproductive groups of either sex. Socially induced infertility in both non-reproductive males and females does not result from a reduced pituitary secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears to result from an inhibition of reproductive behaviour in these obligate outbreeders. The African mole-rats exhibit a continuum of socially induced infertility with differing social species inhabiting regions of varying degrees of aridity. In this continuum a transition from a predominantly behavioural repression in a social mesic-adapted species through to complete physiological suppression lacking incest avoidance in an arid-adapted eusocial species occurs in this endemic African family of rodents.     

Studies on rat ovarian receptors for lutropin (luteinizing hormone). Interaction with beta-subunit of sheep lutropin.

By using radioimmunoassay, the interaction of sheep lutropin (luteinizing hormone, LH) beta-subunit with rat ovarian receptors was investigated. The binding of beta-subunit was specific, although of much lower order than that of lutropin. Sheep lutropin beta-subunit effectively inhibited the binding of human choriogonadotropin (chorionic gonadotropin, gCG) to the ovary, showing that both occupy the same sites. The binding of sheep lutropin beta-subunit to ovary was not followed by any detectable increase in cyclic AMP. The ovarian response to lutropin in terms of cyclic AMP production was inhibited in the presence of free beta-subunit. The alpha-subunit of lutropin, when used at concentrations where contamination with whole lutropin was negligible, enhanced the degree of binding of beta-subunit; this did not lead to increased cyclic AMP in the tissue. Surprisingly, the binding of beta-subunit in vitro was drastically decreased by the prior removal of all endogenous rat lutropin bound to receptors. The implications of these data are discussed in the light of the reported biological activity of the beta-subunit.     

Variants of the CLOCK gene affect the risk of idiopathic male infertility in the Han-Chinese population

Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) has been reported to play a critical role in sperm function and male fertility. The aim of this study was to determine whether variants of the CLOCK gene are involved in idiopathic male infertility. The study included 478 idiopathic infertile men and 194 fertile controls who completed physical examinations. Each subject donated 5?ml of peripheral blood and a sample of semen in the ejaculate. An aliquot of each blood sample was used to separate the serum for the measurement of testosterone as well as follicular stimulating hormone (FSH) using the standard radioimmunoassay. The rest of the blood samples was used to extract the DNA for the assay of three tagging single-nucleotide polymorphisms of CLOCK gene, viz., rs1801260, rs3817444 and rs3749474, using the real-time fluorescence quantitative PCR. The ejaculate of each subject was used for semen analysis by computer-assisted semen analysis system. The results indicated: (a) the variant rs1801260 associated with normal semen parameters was linked to a significant increase in the risk of idiopathic infertility, (b) the variant rs3817444 associated with both normal and abnormal semen parameters also indicated an increased risk of idiopathic infertility, and (c) the variants rs3749474 associated with both normal and abnormal semen parameters, on the other hand, conferred no significant risk for male infertility. Furthermore, elevated serum testosterone and FSH levels were correlated with the three variants of CLOCK gene in idiopathic infertility. The findings demonstrate that the human subjects with variants of the CLOCK gene are associated with idiopathic male infertility and therefore may be applied as a risk factor of male infertility.     

Chemosensory stimulation of luteinizing hormone secretion in male Siberian hamsters (Phodopus sungorus)

Male Siberian hamsters (Phodopus sungorus) housed in long days (LD), but not short days (SD) release luteinizing hormone (LH) when exposed to females. This study examined whether this response is specific to a female and identifies the source of a stimulus that induces LH release. Serum concentrations of LH, testosterone (T), follicle stimulating hormone (FSH), and cortisol were examined in all experiments. T concentrations mirrored the LH response; FSH and cortisol were unchanged in response to all stimuli. Exposure to an LD female, irrespective of her reproductive status, but not an SD female, elicited LH release. Exposure to another male did not trigger LH release. Males released LH when allowed physical contact with an anesthetized female, but not when separated from a normally active female, suggesting that tactile or nonvolatile chemosensory stimuli elicit LH release. Urine and secretions collected from the vagina as well as oral, midventral, perineal, and rectal glands, elicited marked behavioral responses in male P. sungorus. Despite these behavioral responses, only feces from females elicited LH release in males. Males released LH in response to feces extracted from the rectum and to cotton swabs that had been rubbed against the rectal mucosa, suggesting that a component of rectal secretions may trigger LH release in male Siberian hamsters. Taken together, these data and previous data from our laboratory indicate that both the production of and the response to a pheromone that triggers the selective release of LH is regulated by day length.     

Steady-state amounts of alpha- and luteinizing hormone (LH) beta-subunit messenger ribonucleic acids are uncoupled from pulsatility of LH secretion during sexual maturation of the heifer.

Our primary objective for this study was to determine whether steady-state amounts of alpha- and LH beta-subunit mRNAs in the anterior pituitary are altered during sexual maturation in the bovine female. A secondary objective was to determine whether 17 beta-estradiol (E2) alters amounts of LH subunit mRNAs before onset of puberty. Heifers (7 mo old) were assigned to one of three treatments: 1) ovariectomized (OVX, n = 16); 2) OVX and administered E2 (OVXE, n = 16); or 3) ovary-intact (INTACT, n = 20). Pituitaries were collected at an estimated 120 days before onset of puberty (prepuberty) or 25 days before onset of puberty (peripuberty). Six INTACT heifers were used to determine time of puberty during the experimental period, and their pituitaries were collected 40 h after administration of prostaglandin F2 alpha (postpubertal INTACT group). Relative amounts of mRNAs for LH subunits in each pituitary were determined by Northern analysis and scanning densitometry. Amounts of alpha- and LH beta-subunit mRNAs were lower in pituitaries of INTACT heifers and OVXE heifers, regardless of stage of sexual maturation, than in those of OVX heifers. Amounts of alpha-subunit mRNA were similar in OVXE and INTACT heifers regardless of stage of sexual maturation. Amounts of LH beta-subunit mRNA did not change during sexual maturation in heifers in the INTACT group. Concentrations of E2 were higher and LH beta-subunit mRNA were lower in heifers from the prepubertal OVXE group than in heifers in all other treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex differences in pituitary LH storage and release in LHRH-stimulated pubertal rats

Summary This study investigates the relationship between pituitary LHRH responsiveness and the depletion of LH in pubertal rats. The anterior pituitaries of 7-week-old rats of both sexes were stimulated for a maximum of 24 h with either a continuous, or pulsatile exposure to LHRH in vitro. Immunohistochemical examination revealed that most LH-cells in females became depleted of immunoreactive material, regardless of the mode of LHRH administration. In contrast, the majority of LH-cells in the male gland retained a strong immunostaining intensity. Radioimmunoassay showed that the initial pituitary LH content was significantly lower in the female rats (P< 0.001), but, even so, they released a higher percentage of stored LH in response to LHRH stimulation in vitro. A similar result was also obtained after a single injection of LHRH in vivo. Thus, the lower LH content and higher LHRH responsiveness of the female pituitary explain why LHRH treatment induced a pronounced LH depletion in this sex. These results are discussed in relation to available data on heightened LH secretion in maturing female rats.     

Androgens positively regulate follicle-stimulating hormone beta-subunit mRNA levels in rat pituitary cells

We have shown previously that androgens negatively regulate LH alpha and beta-subunit mRNA levels, but have little or no effect on FSH beta mRNA levels in rats in vivo. In contrast, estrogen negatively regulates all three gonadotropin subunit mRNA levels in vivo. We have examined the effects of these sex steroids on gonadotropin subunit synthesis directly at the level of the pituitary gland by using cultured rat pituitary cells. Adult female and male rat pituitaries were dissected, dispersed enzymatically, and maintained in culture for 2 days. At that time, cells were treated for varying lengths of time with either medium alone or sex-steroid hormone treatments (estradiol or testosterone). Dose-response and time-course experiments were performed. Cells were then harvested and total RNA was extracted. Gonadotropin subunit mRNA levels were assessed by blot hybridization techniques. Sex-steroid hormones were added to achieve final concentrations ranging from 10(-12) to 10(-6) M for dose response experiments and 10(-8) M for time-course experiments. Testosterone treatment (10(-8) M) increased FSH beta mRNA levels 3-fold in females (P less than 0.01) and males (P less than 0.05), but had no effect on alpha or LH beta mRNA levels in either sex. Dose-related increases in FSH beta mRNA levels with increasing concentrations of testosterone were observed in both female and male pituitary cell cultures. Time-course studies revealed that the testosterone-stimulated increases in FSH beta mRNA levels are statistically significant by 12 h and 6 h after hormone addition in female and male cultures, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

达英-35治疗多囊卵巢综合征合并不孕症的疗效及对患者血清FSH、LH、TOS、TAS水平的影响

摘要 目的：研究达英-35治疗多囊卵巢综合征合并不孕症的疗效及对患者血清卵泡刺激素(FSH)、促黄体生成素(LH)、总氧化态(TOS)、抗氧化态(TAS)水平的影响。方法：选取2015年8月至2016年7月我院收治的76例多囊卵巢综合征合并不孕症患者,根据随机数字法分为观察组和对照组,38例每组。对照组使用克罗米芬,观察组在此基础上加以达英-35。比较两组患者临床疗效,治疗前后血清FSH、LH、TOS、TAS水平、卵泡数、卵巢体积、体重指数的变化及不良反应的发生情况。结果：治疗后,观察组临床总有效率显著高于对照组[89.47%(34/38) vs. 60.53%(23/38)](P<0.05);两组患者的血清FSH、LH、TOS水平、卵泡数、卵巢体积、体重指数明显减少较治疗前均显著降低(P<0.05),而血清TAS水平较治疗前显著上升(P<0.05),且观察组的血清FSH、LH、水平明显低于对照组(P<0.05),而血清TAS水平显著高于对照组(P<0.05)。观察组和对照组的不良反应的发生率比较无明显差异(P>0.05)。结论：达英-35治疗多囊卵巢综合征合并不孕症患者能有效提高患者的临床疗效和改善其临床症状,且安全性高,这可能与其有效改善患者血清FSH、LH、TOS、TAS水平有关。     

Association of the (TAAAA)n repeat and Asp327Asn polymorphisms in the sex hormone-binding globulin (SHBG) gene with idiopathic male infertility and relation to serum SHBG concentrations

Sex hormone binding globulin (SHBG) is involved in delivering sex hormones to target tissues. We investigated the association between the (TAAAA)n repeat polymorphism, and Asp327Asn polymorphism in the SHBG gene with semen quality and idiopathic male infertility. We studied 168 men with idiopathic infertility [oligoasthenoteratozoospermia (OAT)] and equal number of age-matched normal controls. The serum levels of SHBG, reproductive and thyroid hormones, and Inhibin B were measured. Semen parameters were also assessed. The genotype assays for the SHBG polymorphism were done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Baseline SHBG levels tended to be lower in infertile men (21.1±7.2nmol/l) compared to normal fertile men (24.7±7.9nmol/l). SHBG levels tended to be higher among the subjects with the Asn/Asn (25.84±3.6nmol/l) and S/S (24.50±5.4nmol/l) genotypes compared to subjects with the Asp/Asn (24.38±3.2nmol/l) and L/L (18.44±4.2nmol/l) genotypes of the SHBG gene. The genotype frequencies of Asp/Asp were 80.9% in cases and 71.4% in controls (P=0.001). The variant Asp/Asn genotype was associated with a more than 50% reduced risk of infertility (OR: 0.46, 95% CI: 0.25-0.80, P=0.001). Genotype analysis demonstrated six SHBG (TAAAA)n alleles with 6-11 repeats. Long SHBG (TAAAA)n alleles (>8 repeats) were at greater frequency in infertile men than fertile subjects (P=0.001), whereas short SHBG (TAAAA)n alleles (≤8 repeats) tended to be more frequent in fertile men than cases (P=0.001). Men with the 9/X TAAAA repeat genotype displayed a 2.82-fold increased risk of infertility (95% CI: 1.27-4.79, P=0.01). There were strong and significant positive correlations between plasma SHBG and sperm count (r=0.672, P=0.01), sperm motility (r=0.721, P=0.01) and sperm morphology (r=0.574, P=0.02). We concluded that the SHBG Asp237Asn and (TAAAA)n polymorphisms may influence SHBG levels and as a result, male infertility. Multicenter large scale studies are warranted to better elucidate the role of SHBG gene polymorphism in male infertility.     

The effects of luteinizing hormone, oestrogen and ovariectomy on the agonistic behaviour of female Quelea quelea

Previous work with male Quelea showed that agonistic behaviour in relation to individual distance is controlled by luteinizing hormone (LH), rather than by testosterone, and that males are more aggressive than females. Experiments with female groups are reported which show that: (a) LH injections increase aggressive encounter frequency; (b) ovariectomy in the breeding season (but not outside it) also increases encounter frequency; and (c) oestrogen injections decrease encounter frequency. The effects of LH were shown to be specific to agonistic responses rather than mediated through changes in activity. Correlations between changes in natural hormone levels and encounter frequency support the injection findings. These results are consistent with the hypothesis that LH controls aggressive encounters over individual distance in the female as in the male and that oestrogenic inhibition of this LH-mediated aggressiveness is a cause of female subordination and the lower encounter frequency found in female groups. The annual cycle of encounter frequency is described and the significance of different systems of hormonal control is discussed.     

The essential roles of TGFB1 in reproduction

Transforming growth factor beta 1 (TGFB1) is implicated as a key regulator of the development and cyclic remodelling characteristic of reproductive tissues. The physiological significance of TGFB1 in reproductive biology and fertility has been extensively examined in Tgfb1 null mutant mice. Genetic deficiency in TGFB1 causes perturbed functioning of the hypothalamic–pituitary–gonadal axis, inhibiting luteinising hormone (LH) synthesis and leading to downstream effects on testosterone production in males and estrous cycle abnormalities in females. Oocyte developmental incompetence, accompanied by early embryo arrest as well as altered pubertal mammary gland morphogenesis are observed. In addition to LH and testosterone deficiency, male Tgfb1 null mice demonstrate complete inability to mate with females, associated with failure to initiate and/or sustain successful penile intromission or ejaculation. These studies demonstrate the profound significance of TGFB1 in male and female reproductive physiology, and provide a foundation for exploring the significance of this cytokine in human infertility and sexual dysfunction.     

Module dynamics of the GnRH signal transduction network

We analyse computational modules of a frequency decoding signal transduction network. The gonadotropin releasing hormone (GnRH) signal transduction network mediates the biosynthesis and release of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The pulsatile pattern of GnRH production by the hypothalamus has a critical influence on the release and synthesis of gonadotropins in the pituitary. In humans, slower pulses lead to the expression of the beta-subunit of the LH protein and cause anovulation and amenorrhea. Higher frequency pulses lead to expression of the alpha subunit and a hypogonadal state. The frequency sensitivity is a consequence of the structure of the GnRH signal transduction network. We analyse individual components of this network, organized into three network architectures, and describe the frequency-decoding capabilities of each of these modules. We find that these modules are comparable to simple circuit elements, some of which integrate and others which perform as frequency sensitive filters. We propose that the cell computes by exploiting variation in the time scales of protein activation (phosphorylation) and gene expression.     

Ovarian Steroids: The Good,the Bad,and the Signals that Raise Them

Ovarian steroid production and subsequent local steroid-mediated signaling are critical for normal ovarian processes, including follicle growth, oocyte maturation, and ovulation. In contrast, elevated steroidogenesis and/or increased steroid signaling in the ovary can lead to profound ovarian pathology, such as polycystic ovarian syndrome, the leading cause of infertility in reproductive age women. Through the use of several in vitro and animal models, great strides have been made toward characterizing the mechanisms regulating local steroid production and action in the ovary. Examples of this progress include insights into luteinizing hormone (LH)- and growth factor-mediated signaling, steroidogenic acute regulatory protein (StAR) activation, and both genomic and nongenomic steroid-mediated signaling in somatic and germ cells, respectively. The following review will address these advances, focusing on how this rapidly expanding knowledge base can be used to better understand female reproduction, and to further improve treatments for common diseases of infertility.     

Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion

Transgenic (TG) female mice, expressing a chimeric bovine luteinizing hormone (LH) beta-subunit/human chorionic gonadotropin beta-subunit COOH-terminal extension (bLHbeta-CTP) gene, produce high levels of circulating LH and serve as a model for functional ovarian hyperandrogenism and follicular cysts. We report here that obesity is a typical feature of these female mice. The mean body weight of the bLHbeta-CTP females was significantly higher than in controls at, and beyond 5 wk of age, and at 5 mo, it was 32% increased. At this age, the amount of white adipose tissue in the bLHbeta-CTP females was significantly increased, as reflected by the weight difference of the retroperitoneal fat pad. In addition, the expression of leptin mRNA in white adipose tissue of the TG females was elevated about twofold. Serum leptin and insulin levels, and food intake, were also increased significantly in the TG females. Brown adipose tissue (BAT) thermogenic activity, as measured by GDP binding to BAT mitochondria, was reduced (P < 0.05). Ovariectomy at the age of 3 wk totally prevented the development of obesity. In summary, the present results show that intact female bLHbeta-CTP mice are obese, have increased food consumption, and reduced BAT thermogenic activity. The weight gain can be explained partly by elevated androgens but is probably also contributed to the increased adrenal steroidogenesis. Hence, the bLHbeta-CTP mice provide a useful model for studying obesity related to elevated LH secretion, with consequent alterations in ovarian and adrenal function.     

Differential effects of the perinatal steroid environment on three sexually dimorphic parameters of the rat brain

Gonadectomy of male rats was performed at 0, 6-7 (6h), 12-13 (12h), or 24 h postnatally in order to examine the influence of testosterone exposure on sexual differentiation of the brain. The indices examined were: the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) titers following estradiol benzoate (EB) and progesterone (P) administration. Control animals were sham-operated at 0 h and gonadectomized at 29 days of age (sham). A decrease in the percentage of males with elevated plasma LH levels following P was found with increasing delay before gonadectomy. Significant (P less than 0.001) differences existed in the amplitude of plasma LH titers 5 h following P administration between sham, 0 h, and 6 h groups. Follicle-stimulating hormone was also elevated in all neonatally gonadectomized male groups following P administration, but there was no difference between the groups. Volume of the SDN-POA was significantly (P less than 0.001) smaller in all gonadectomized males when compared to that of sham-operated males, but no differences existed between males gonadectomized at the different hours postpartum. In female rats gonadectomized at 0 h (F0h), LH levels were elevated 5 h following P, but only to a magnitude of 36% of that of sham-operated controls (P less than 0.001). Volume of the SDN-POA of the F0h group was significantly reduced (P less than 0.05) when compared to that of sham females. Thus, in males, the presence of the tests prenatally may be responsible for the initiation of masculinization of LH release mechanisms and the SDN-POA, but both require further androgen exposure for their completion. In addition, the LH and FSH regulating systems show a differential sensitivity to the steroid hormone environment during development that shapes the animal's response to steroid as an adult.