Neurogenic bladder and neuroendocrine abnormalities in Pol III-related leukodystrophy.

BACKGROUND: Pol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations. We report the unique neurologic presentation of the micturition dysfunction in Pol III-related leukodystrophy and describe the novel endocrine abnormalities in this entity. CASE PRESENTATION: A 32-year-old Caucasian female exhibited chronic urinary incontinence that commenced at the age of 7 years and remained the unexplained symptom more than two decades before the onset of progressive neurologic decline. A transient growth failure and absent sexual development with hypoprolactinemia appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic evaluation performed only in the patient's thirties, confirmed the diagnosis of 4H leukodystrophy as the only cause of the micturition disturbance. CONCLUSION: The report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated also as a possible 4H leukodystrophy, thus alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy.

[Number of teeth and hormonal profile of postmenopausal women with osteoporosis, osteopenia and normal bone mineral density--a preliminary study]. / Liczba zebów oraz profil hormonalny u kobiet po menopauzie z osteoporoza, osteopenia oraz prawidlowa gestoscia tkanki kostnej--badania wstepne.

UNLABELLED: Profound hypoestrogenism causes increased risk of osteoporosis and bone fracture in menopause. This period of women life is also characterized by decrease number of teeth and deterioration of oral cavity health. AIM: The aim of the study was to assess the number of teeth, hormonal profile (Follicle-stimualting hormone (FSH), estradiol (E2), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) and the bone mineral density (BMD) of the lumbar part of the spine in postmenopausal women with osteoporosis, osteopenia and normal BMD. The next step of the study was to determine whether there was a correlation between vertebral mineral bone density, the hormonal profile and the number of teeth. MATERIALS AND METHODS: A total number of 47 women was involved in the study. Based on the results of densitometry tests (DEXA) of vertebral column the subjects were divided into 3 groups: 10 with osteoporosis, 20 with osteopenia and 17 with normal BMD. All the subjects had undergone a hormonal assessment which included blood serum estimation for FSH, E2, DHEA-S and T levels. Also the total number of teeth present was recorded. RESULTS: Serum estradiol and testosterone levels in postmenopausal women were found to be positively correlated with the number of teeth present. A negative correlation was found between age and the number of maxillary teeth in postmenopausal women with osteopenia. There was no influence of serum FSH, estradiol, testosterone and DHEA-S levels on vertebral BMD loss in postmenopausal women. There was no correlation between teeth number and BMD of vertebral column. CONCLUSIONS: Serum levels of estradiol and testosterone in postmenopausal women positively correlate with teeth numbers. Age is the main risk factor for teeth loss in postmenopausal women.

A factor analysis approach to examining relationships among ovarian steroid concentrations, gonadotrophin concentrations and menstrual cycle length characteristics in healthy, cycling women.

STUDY QUESTION: How are ovarian steroid concentrations, gonadotrophins and menstrual cycle characteristics inter-related within normal menstrual cycles? SUMMARY ANSWER: Within cycles, measures of estradiol production are highly related to one another, as are measures of progesterone production; however, the two hormones also show some independence from one another, and measures of cycle length and gonadotrophin concentrations show even greater independence, indicating minimal integration within cycles. WHAT IS KNOWN ALREADY: The menstrual cycle is typically conceptualized as a cohesive unit, with hormone levels, follicular development and ovulation all closely inter-related within a single cycle. Empirical support for this idea is limited, however, and to our knowledge, no analysis has examined the relationships among all of these components simultaneously. STUDY DESIGN, SIZE, DURATION: A total of 206 healthy, cycling Norwegian women participated in a prospective cohort study (EBBA-I) over the duration of a single menstrual cycle. Of these, 192 contributed hormonal and cycle data to the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects provided daily saliva samples throughout the menstrual cycle from which estradiol and progesterone concentrations were measured. FSH and LH concentrations were measured in serum samples from three points in the same menstrual cycle and cycle length characteristics were calculated based on hormonal data and menstrual records. A factor analysis was conducted to examine the underlying relationships among 22 variables derived from the hormonal data and menstrual cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Six rotated factors emerged, explaining 80% of the variance in the data. Of these, factors representing estradiol and progesterone concentrations accounted for 37 and 13% of the variance, respectively. There was some association between measures of estradiol and progesterone production within cycles; however, cycle length characteristics and gonadotrophin concentrations showed little association with any measure of ovarian hormone concentrations. LIMITATIONS, REASONS FOR CAUTION: Our summary measures of ovarian hormones may be imprecise in women with extremely long or short cycles, which could affect the patterns emerging in the factor analysis. Given that we only had data from one cycle on each woman, we cannot address how cycle characteristics may covary within individual women across multiple cycles. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are generalizable to other healthy populations with typical cycles, however, may not be applicable to cycles that are anovulatory, extreme in length or otherwise atypical. The results support previous findings that measures of estradiol production are highly correlated across the cycle, as are measures of progesterone production. Estradiol and progesterone concentrations are associated with one another, furthermore. However factor analysis also revealed more complex underlying patterns in the menstrual cycle, highlighting the fact that gonadotrophin concentrations and cycle length characteristics are virtually independent of ovarian hormones. These results suggest that despite integration of follicular and luteal ovarian steroid production across the cycle, cycle quality is a multi-faceted construct, rather than a single dimension. STUDY FUNDING/COMPETING INTEREST(S): The EBBA-I study was supported by a grant from the Norwegian Cancer Society (49 258, 05087); Foundation for the Norwegian Health and Rehabilitation Organizations (59010-2000/2001/2002); Aakre Foundation (5695-2000, 5754-2002) and Health Region East. The current analyses were completed under funding from the National Institutes of Health (K12 ES019852). No competing interests declared.

Steroidogenic activity of liposomal methylated resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model.

PURPOSE: Steroid hormone secretion is one of the key functions of granulosa cells (GCs). Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. The methoxy derivative of resveratrol (DMU-212) was demonstrated to be more lipophilic, and therefore of greater bioavailability. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model. METHODS: DMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to the liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze the expression of steroidogenesis-related genes. Finally, the western blot technique was used to analyze the effect of lipDMU-212 and FSH treatments on CYP11A1 and HSD3B1 protein levels. RESULTS: lipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing the expression of CYP11A1, HSD3B1, StAR, CYP17A1, CYP19A1, and HSD17B1 genes. We have also shown that lipDMU-212, used alone and in combination with FSH, significantly increased the expression of the HSD3B1 and CYP11A1 proteins in GCs. Furthermore, our study suggests that lipDMU-212 increases FSH activity. CONCLUSIONS: This is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.

In vitro growth and steroidogenesis of dog follicles are influenced by the physical and hormonal microenvironment.

The present study examined the influences of the physical and hormonal microenvironment on in vitro growth and steroidogenesis of dog follicles. Follicles were enzymatically isolated and individually encapsulated in 0.5% (w/v; n=17) or 1.5% (n=10) alginate and cultured with 0.5 IU/ml equine chorionic gonadotropin for 192 h. In a separate experiment, follicles were encapsulated in 0.5% alginate and cultured with 0 (n=22), 1 (n=23), 10 (n=20) or 100 (n=21) µg/ml FSH for 240 h. Follicle diameter and steroid production were assessed every 48 h in both studies. Follicles encapsulated in the 0.5% alginate grew faster (P<0.05) than those cultured in the 1.5% concentration. Oestradiol (E(2)) and progesterone (P(4)) increased consistently (P<0.05) over time, and follicles in the 1.5% alginate produced more (P<0.05) P(4) than those in the 0.5% solution. Follicles cultured in the highest FSH concentration (100 µg/ml) increased 100% in size after 240 h compared with 50 to 70% in lower dosages. E(2) concentration remained unchanged over time (P>0.05) across FSH dosages. However, P(4) increased (P<0.05) as culture progressed and with increasing FSH concentration. Results demonstrate that dog follicles cultured in alginate retain structural integrity, grow in size and are hormonally active. Lower alginate and increasing FSH concentrations promote in vitro follicle growth. However, the absence of an E(2) rise in follicles cultured in FSH alone suggests the need for LH supplementation to support theca cell differentiation and granulosa cell function.

Assessment of the biopotency of follitropin alfa and lutropin alfa combined in one injection: a comparative trial in Sprague-Dawley rats.

BACKGROUND: The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection. METHODS: The biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2 degrees C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion. RESULTS: FSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C for not more than 1 h prior to injection. CONCLUSION: Mixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH.

Influence of Hormones on Sjögren's Syndrome.

Sjögren's syndrome (SS) is an immune system oral disorder that is characterized generally by dry mouth and eyes. In this review, SS classification, presentation and pathogenesis are briefly discussed. Moreover, the epidemiology of SS regarding sex, age and association with other complications are also presented. This review also addresses the interactions between endocrine axes and SS, and the important findings up to regarding hormone treatment of this syndrome. The main hormones discussed in this review includes Adrenocorticotropic hormone (ACTH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Thyroid-stimulating hormone (TSH), and prolactin.

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

Context: Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1ß, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). Objectives: We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. Design and Participants: In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. Outcome Measures: The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Results: Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). Conclusion: IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate.

Effects of progesterone on estrogen-induced gonadotropin release in male rhesus macaques.

The effects of progesterone (P) on estrogen (E)-induced gonadotropin release were studied in 10 adult male rhesus macaques castrated more than 2 yr earlier. The intent was to determine whether physiological levels of P (approximately 400 pg/ml) found in the systemic circulation of intact males would block E-induced gonadotropin release and whether the responses of castrated males were similar to those of castrated females with and without pretreatment with 17 beta-estradiol (E2). Different doses of P were administered in Silastic capsules (0.3, 4.0, and 5.0 cm) implanted sc. A 0.3-cm implant maintained serum P levels at about 400 pg/ml (equivalent to physiological levels in intact males); 5.0-cm implants produced serum levels of about 4.0 ng/ml (similar to luteal phase levels in females). In male monkeys treated for approximately 3 weeks with E2, only the highest dose (approximately 4.0 ng/ml) of P blocked FSH induced by estradiol benzoate (E2B). LH was blocked in one third of the animals thus treated. The same P dose was ineffective in blocking E2-induced LH release in spayed females pretreated with E2, but did block FSH release. Gonadectomized males and females not treated beforehand with E2 released LH in response to an E2B challenge, but FSH was not elevated in the peripheral circulation under these experimental conditions. These results suggest that luteal phase levels of P block E2-induced FSH release in gonadectomized males and females. With the same treatment regimens, P blocks E2 action in some males, but all females responded to E2B by releasing LH. These data also suggest that estrogen priming is necessary for FSH, but not LH, release in adult rhesus macaques of both sexes. The prerequisite of E treatment for the induction of positive feedback appears to be associated with the level of gonadotropin suppression before E2B treatment.

Effect of bacitracin and polyamines on follicle-stimulating hormone binding to membrane-bound and detergent-solubilized bovine calf testis receptor.

We have examined the effects of bacitracin and several polyamines on the interaction of 125I-human FSH (125I-hFSH) with membrane-bound receptors (MR) or detergent-solubilized receptors (DSR) derived from bovine calf testes. Binding of 125I-hFSH to either calf testis MR or DSR was inhibited by bacitracin in a dose-related manner. Inhibition of 125I-hFSH binding to either MR or DSR was due to a decrease in the apparent affinity constant (Ka) of receptor for FSH. FSH binding inhibition by bacitracin was significantly greater with the MR (ED50 = 5.9 mM) than with the DSR (ED50 = 25 mM). Bacitracin was a more potent inhibitor of binding than the polyamines at equimolar concentrations in both MR and DSR systems. The inhibitor potency of the polyamines when using DSR was related to chain length and the number of amino groups present (spermine greater than spermidine greater than putrescine). Although it was not possible to ascertain the mechanism of binding inhibition, our results demonstrate a direct effect of bacitracin and polyamines on the interaction of FSH with testis receptors.

Steroid control of gonadotropin secretion and ovarian function in heifers.

The failure of anti-steroid treatments to induce multiple ovulations in cattle in a repeatable way, prompted us to examine the role of the gonadal steroids in the control of gonadotropin secretion in this species. A better understanding of the control of gonadotropin secretion in the cow would assist in the development of treatments to control prolificacy. Groups of six heifers were implanted with one of three sizes of estradiol (E2) implant on day 9 of a synchronized estrous cycle, and five control heifers received empty implants. All heifers were ovariectomized during the luteal phase of the subsequent estrous cycle and given progesterone-releasing intravaginal devices (PRID). Blood samples were taken every 10 min for 12 h with PRIDs and for 6 h after PRID withdrawal, for the measurement of LH and FSH concentrations. The two larger implant sizes (increasing E2 concentrations to 7.4 and 18.7 pg/ml plasma during the luteal phase of the cycle) decreased ovulation rate, the number of large follicles, and luteal weight. After ovariectomy, the three implant sizes produced E2 concentrations comparable with those during the luteal and follicular phases of the estrous cycle and at estrus (1.5, 4.4, and 10.5 pg/ml, respectively). E2 alone decreased mean LH and FSH concentrations and LH pulse amplitude, whereas progesterone alone reduced mean gonadotropin concentrations and LH pulse frequency. Only in the presence of progesterone did E2 decrease LH pulse frequency. Steroid concentrations which mimicked those of the luteal and follicular phases of the cycle produced luteal- and follicular-phase patterns of LH and FSH secretion. These results confirm that E2 and progesterone are important regulators of gonadotropin secretion in cattle, and question the role of inhibin in this respect.

Gonadal regulation of gonadotropin subunit gene expression: evidence for regulation of follicle-stimulating hormone-beta messenger ribonucleic acid by nonsteroidal hormones in female rats.

Gonadectomy results in a rise in gonadotropin secretion and subunit gene expression, although the relative contributions of declining gonadal hormones or increasing hypothalamic GnRH secretion are uncertain. To further delineate the roles of the hypothalamus and gonads in regulation of gonadotropin gene expression, male and female rats were castrated and gonadotropin subunit messenger RNA (mRNA) concentrations measured 2, 7, 14, or 21 days (d) later. In males, FSH beta mRNA was maximal (2-fold increase) by 7 d while peak levels of alpha (3-fold) and LH beta (3-fold) were seen by 14 d. Testosterone (T) replacement restored all three subunit mRNA concentrations to intact values. In females, FSH beta mRNA also reached plateau levels (8-fold increase) earlier than alpha (3-fold) or LH beta (11-fold). When female rats ovariectomized 7 days earlier were given estradiol (E2) and progesterone (P) implants for up to 14 d, suppression of alpha and LH beta to intact levels was observed. However, FSH beta mRNA concentrations only decreased to 67% of castrate values, and remained 2- to 3-fold higher than levels in intact female rats. Female rats were also given E2 replacement at the time of ovariectomy. LH beta mRNA was maintained at intact levels for 14 days while alpha and FSH beta showed partial castration responses (2-fold and 3-fold, respectively). Finally, to determine whether E2 and P regulate gonadotropin subunit expression directly or by reducing GnRH secretion, female rats were ovariectomized and immediately replaced with E2, P, or E2 + P in the presence or absence of a GnRH antagonist (A) for 2 d. alpha mRNA was increased (2-fold) by E2 but not by E2 + A suggesting that E2 requires the presence of GnRH to increase alpha mRNA. P alone was ineffective, but both E2 and A prevented the LH beta mRNA response to ovariectomy. The effects of E2 and A were not additive, suggesting that E suppresses LH beta mRNA by inhibiting the increase in GnRH secretion. In contrast, the FSH beta mRNA response to ovariectomy was only partially suppressed by E2, E2 + P, or E2 + P + A. These data indicate that in castrate males, replacement of T suppresses all three subunit mRNAs to intact levels. However, replacement of E2 to ovariectomized females did not prevent the increase in alpha and FSH beta mRNAs. In female rats, LH beta mRNA is predominantly regulated by GnRH. alpha mRNA expression is also mainly regulated by GnRH, and E2 appears to augment GnRH action on alpha mRNA expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Naloxone administration does not affect gonadotropin secretion in agonadal men either basally or during testosterone treatment.

Naloxone administration has no effect on plasma gonadotropin levels of agonadal men. The present study was designed to evaluate whether testosterone replacement therapy could restore LH responsiveness to naloxone in such men. We measured plasma LH and FSH levels at 15-min intervals during naloxone infusion (8 mg in 1 min followed by 12 mg in 3 h) and for the following 3 h in a group of agonadal men both before and after at least 2 months of three different schedules of testosterone replacement therapy: 1) testosterone undecanoate, 40 mg three times a day by mouth; 2) testosterone enanthate 200 mg im every 2 weeks; and 3) testosterone enanthate 100 mg im once a week. Mean plasma gonadotropin levels as well as LH pulse frequency did not vary during naloxone infusion vs. placebo either basally or during each testosterone regimen. These results suggest that long term testosterone therapy does not affect the altered opioid modulation of gonadotropin secretion which is present in agonadal men.

Progesterone inhibits the estrogen-induced gonadotropin surge in the rhesus monkey independent of endogenous opiates.

Administration of an estrogen challenge during the luteal phase, a time when progesterone concentrations are elevated, fails to elicit a gonadotropin-positive feedback response. The purpose of the present study was to determine if endogenous opiates are involved in the mechanism by which progesterone blocks the estrogen-induced gonadotropin surge in monkeys. To this end, rhesus monkeys in the luteal phase were pretreated with either saline or various regimens of nalmefene, a long-acting opiate antagonist, before being given an estrogen challenge. Three groups of animals were given nalmefene (10 mg, iv) every 12 h beginning 24, 48, or 96 h before an estrogen challenge and continued until 48 h after the start of the estrogen challenge. A fourth group received a continuous sc infusion of nalmefene (20 mg/day) via osmotic minipumps beginning 48 h in advance of the estrogen challenge. In a second experiment, monkeys in the follicular phase received progesterone implants at the time of an estrogen challenge and iv injections of nalmefene every 12 h for 48 h. Gonadotropin and steroid levels were monitored in both experiments by collecting blood samples by saphenous venipuncture at intervals of 6-12 h. The majority of luteal phase animals that were pretreated with saline were unresponsive to the estrogen challenge. Only 2 of 16 (12.5%) had an increase in LH concentrations that could be classified as a surge. Animals pretreated with iv nalmefene every 12 h beginning 48 h before the estrogen challenge exhibited a higher incidence of positive feedback responses (8 of 12 or 66.7%). A concomitant FSH surge was observed in 3 of these instances. However, when progesterone concentrations, which declined before the estrogen challenge in the nalmefene-treated group, were supplemented with exogenous progesterone, nalmefene failed to evoke any LH surges. Six of 8 animals that received nalmefene by sc infusion exhibited LH responses. However, the amplitude and duration of these LH responses were diminished, and no FSH responses were observed. Monkeys pretreated with nalmefene for either shorter (24 h) or longer (96 h) periods before the challenge were less responsive (0 responses out of 6 trials and 1 response out of 4 trials, respectively). Nalmefene was equally ineffective in preventing progesterone inhibition of the estradiol-induced LH surge in follicular phase animals (0 of 15 animals had LH surge). These results indicate that nalmefene antagonism of endogenous opiates does not enable estrogen to exert positive feedback effects on LH release when progesterone levels are high, such as during the luteal phase or after progesterone administration.(ABSTRACT TRUNCATED AT 400 WORDS)

A tetrapeptide within a receptor-binding region of human follicle-stimulating hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in Sertoli cells.

In a previous study, we showed that binding of FSH by cultured rat Sertoli cells significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was observed when proteoliposomes enriched with bovine calf testis follicle-stimulating hormone (FSH) receptors were stimulated with FSH. In the present study, we screened a series of overlapping synthetic peptide amides, representing the entire primary structure of the beta-subunit of hFSH, for their effects on sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+ exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200 microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium-dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH-beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli cells was enhanced in a concentration-related manner when extracellular sodium was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH-beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical properties of the testicular follitropin-receptor system.

The interaction of FSH with membrane receptors from rat and calf testis has been studied in some detail. The FSH receptor has been solubilized through use of the nonionic detergent Triton X-100 and highly purified by affinity chromatography on Affigel-10 coupled to ovine FSH. Hormone binding activity of the solubilized receptor has been preserved for extended periods through use of the structure-stabilizing agent glycerol. Other components of the FSH testes receptor system including the guanyl nucleotide binding protein and adenylate cyclase have been solubilized by nonionic detergents and also found to be stabilized by glycerol. FSH binding activity has been observed in testes cytosol and represents a putative class of receptors prepared from testes in the absence of detergent. The concentration of this buffer-soluble component decreased with age and increased concomitantly with loss of membrane receptors consequent to their down-regulation after administration of exogenous FSH. Phospholipids seem involved in the interaction of FSH with membrane-bound, detergent-solubilized, and buffer-soluble FSH binding activity. Phospholipids may maintain or stabilize a particular receptor conformation necessary for interaction with the hormone. A specific role for GTP seems indicated in regulation of FSH-stimulated adenylate cyclase activity in immature rat testis. Follitropin binding to testes receptor appears modulated by a variety of factors present in serum, testes extracts, follicular fluid, and seminal plasma, which are poorly understood at present. Inhibition of FSH binding by seminal plasma best-fit by a model proposing two hormone binding sites per receptor molecule, where binding to one site decreases the affinity of the other site for FSH. As a result of studies in this and other laboratories, the molecular endocrinology of FSH interaction with testis receptors is becoming increasingly understood.

The relationship of exercise to anovulatory cycles in female athletes: hormonal and physical characteristics.

The objective of this study was to examine the mechanisms by which physical activity affects the menstrual cycle. Women with high, medium, and low levels of physical activity were compared for menstrual function, physical characteristics, and urinary and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol-17 beta, and 2-hydroxyestrone. None of the physical characteristics other than age and muscle area were significantly different in the three groups. The percentage of body fat did not appear to be a factor in the amenorrhea induced by strenuous exercise, as the percent of body fat in all three groups was less than 22%. The group of athletes under strenuous exercise which correlated with oligomenorrhea had decreased serum levels of luteinizing hormone, prolactin, and estradiol-17 beta but elevated levels of 2-hydroxyestrone. These data suggest that anovulatory cycles are correlated with the amount of exercise and increased levels of catechol estrogens. Catecholamines and beta-endorphin elevated by exercise may interact to suppress luteinizing hormone release at the hypothalamic pituitary axis.

Chronic morphine and testosterone treatment: effects on norepinephrine and serotonin metabolism and gonadotropin secretion in male rats.

The effects of sustained-release implants of morphine (M) and/or testosterone (T) on serum gonadotropin levels and norepinephrine (NE) and serotonin (5-HT) metabolism in brain regions were examined. While 4 days of M or 5 mm [corrected] T treatment were without significant effect, the combination dramatically decreased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Castration increased NE content of the mediobasal hypothalamus (MBH), and although M, 5 mm [corrected] T, or their combination significantly reduced NE levels in the MBH, they remained elevated compared to intact or 30 mm [corrected] T-treated rats. Further, in the MBH no differences in normetanephrine (NME) levels, nor in NME:NE ratios, nor 5-HT metabolism were evident. In the preoptic area-anterior hypothalamus, NE or 5-HT metabolism were not altered by castration and M and/or T. These results show that M and T interact to suppress LH and FSH release in the apparent absence of any appreciable effect on hypothalamic monoamines.

Prediction and detection of ovulation.

PIP: This paper reviews and evaluates various methods for the prediction and detection of ovulation, with emphasis on the role this plays in management of infertility and in natural family planning. After spelling out the hormonal events which control the ovulatory process, techniques for ovulation detection and timing are discussed. These fall into 2 classifications: 1) direct assays of gonadotropins or steroid hormones in the serum or urine; and 2) evaluation of peripheral changes preceding, coinciding with, or succeeding ovulation. Since serial hormone assays are not practical in routine clinical practice, clinicians generally rely on peripheral or end-organ changes to determine alteration in circulating steroid hermone levels, but direct assays of gonadotropins and sex steroids would have to supplement these methods to determine the accuracy of commonly performed methods of ovulation detection. Tests based on hormone assays include daily assays of 1) serum or urinary lutienizing hormone (LH), 2) urinary estrogens (or estrogen metabolites) or serum estradiol, and 3) serum progesterone or urinary pregnanediol. Each assay is described in the text. Tests based on peripheral and systemic changes include ]) basal body temperature changes, 2) tests of physical properties of cervical mucus (appearance, spinnbarkheit, ferning, and burn test), 3) tests of the chemical content of cervical mucus (protein constituents and enzymes), 4) endometrial biopsy, 5) vaginal cytology, and 6) saliva sampling (measuring alkaline phosphatase levels which generally increase at time of ovulation). Tests based on hematologic changes, especially the decrease of blood basophil count at ovulation, are also discussed. Among the possible techniques of natural family planning discussed are the calendar method (Ogino-Knaus), the cervical mucus (ovulation) method, and the symptothermic method (basal temperature and calender combined) method.^ieng

Concentration of circulating hormones and metabolism of androgens by human gingiva.

The present study evaluates the relationship between periodontal status, concentration of circulating hormones and metabolism of androgens by human male and female gingiva in vitro. In both male and female patients with healthy gingiva the plasma concentration of gonadotropins (LH and FSH) and steroid hormones (testosterone, androstenedione, estradiol-17 beta, progesterone and cortisol) were in a normal range. However, an alteration in the plasma concentration of progesterone was found in both male and female patients with periodontal pathosis. Both androgens (testosterone and androstenedione) were readily metabolized by human gingiva tissue in vitro. The major pathway of the metabolism of testosterone was via the formation of 17 beta-hydroxy-5 alpha-A-ring reduced androgens (5 alpha-dihydrotestosterone and 3 alpha-, 3 beta-androstanediol). In contrast, androstenedione was metabolized mainly to 17-keto-5 alpha-A-ring reduced (5 alpha-androstanedione, androsterone and epiandrosterone) and 17 beta-oxidoreduced (testosterone) compounds. In addition both substrates were metabolized to 5 beta-A-ring reduced androgens (5 beta-dihydrotestosterone, 5 beta-androstanediol and 5 beta-androstanedione). A significant feature of the metabolism of testosterone and androstenedione by inflamed gingiva was an increase of 5 alpha-A-ring reductase activity (mainly the formation of 5 alpha-dihydrotestosterone and 5 alpha-androstanedione) and 17 beta-oxidoreductase activity (mainly the formation of testosterone from androstenedione). The increase in 5 alpha-reductase activity also showed a significant correlation with the plasma progesterone concentration.