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Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, but the mechanism of anovulation remains obscure. Anovulation in PCOS is characterized by an apparent arrest of antral follicle development at the 5- to 10-mm stage and therefore a failure to enter the preovulatory phase of the cycle. Spontaneous ovulation can occasionally occur, and the disorder can be reversed...
The testis is a complex organ that serves two crucial functions: synthesis and secretion of testosterone and production of a sufficient number of competent spermatozoa to attain fertility. The two functions are strictly correlated in that it is the local action of testosterone on spermatogenesis that determines fertility. Furthermore, spermatogenesis is a dynamic process organized so that, at a...
Na,K-ATPase is an integral plasma membrane enzyme essential for cellular homeostasis. The molecular characterization of Na,K-ATPase has identified three α-subunit isoforms (α 1 , α 2 , and α 3 ) and three β-isoforms in mammals (β 1 , β 2 , and β 3 ). The purpose of this study was to examine the effect of estradiol-17β benzoate (EB) in vivo on protein...
The interaction between SBP and its receptor (SBP-R) inhibits estradiol-induced proliferation of MCF-7 cells (human estrogen-dependent breast cancer) through cAMP and PKA. Thus, SBP can modulate estradiol action in breast cancer, but the implications of this require a more detailed knowledge of the SBP-R. For this reason, we transfected MCF-7 cells with an expression vector carrying the human SBP...
Various pharmacological activities of phytoestrogens have become apparent. High levels of isoflavonoids among Japanese are associated with a low incidence of hormone-dependent cancers, but nothing is known about transfer through the placenta of these compounds. We studied seven young healthy voluntary Japanese women at delivery measuring six phytoestrogen metabolites in maternal and cord plasma and...
ongenital adrenal hyperplasia is a term encompassing a group of genetic defects affecting the biosynthesis of cortisol. Autosomal recessive mutations occurring at any of five different loci inhibit or block the activity of one of the five enzymes required for its formation from cholesterol by the adrenal cortex. Low plasma cortisol from the abnormally low rates of synthesis causes secondary elevation...
Nuclear receptors are ligand-dependent transcription factors. These regulatory proteins control complex gene networks involved in embryonic development, cellular differentiation, and homeostasis. The super-family of nuclear receptors includes receptors for steroid and thyroid hormones as well as for the active derivatives of vitamins A and D. In addition, this family includes many members for which...
Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17α-substituted analogs of 17β-estradiol and their Δ 9(11) -dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative...
ABP/SHBG gene products interact with spermatogenic cells of different species by receptor-mediated mechanism depending on the maturation step (Gerard et al., 1990-95) and are supposed to play a role of paracrine factor in the testis. To elucidate the physiological significance of ABP action on germ cells and because germ cells did not survive without Sertoli cells, we needed to create an experimental...
We are investigating human brain steroidogenesis in healthy and diseased conditions at various stages of development in particular aromatase levels but also related enzymes. Aromatase activity is measured in differentiated and undifferentiated neuroblastoma cell lines (TMN) as well as in normal human postmortem brain samples of different age, gender, and health states for comparison. The undifferentiated...
Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds certain naturally occurring estrogens and androgens with high affinity. Traditionally, its sole function has been thought to be to regulate the free and bound concentrations of those steroid hormones that bind to it. This concept has been a clinically useful one in that the concentration of unbound steroids has proven, in general,...
The formation and function of the corpus luteum (CL) are largely dependent on proper pituitary LH support. However, there is also increasing evidence that steroids produced by the CL act within the CL in an autocrine/paracrine manner. In addition, a number of peptides and eicosanoids also produced locally are involved in the regulation of luteal steroid production. In many species, including the...
Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. The study of Xp duplicated patients demonstrated that sex reversal results from the presence of two active copies of the DSS (Dosage Sensitive Sex reversal) locus. A double dosage of DSS disrupts testis formation, whereas its absence is compatible with a male phenotype, suggesting...
Cathepsin D plays an important role in physiological and pathological processes including cancer invasion and metastasis. Its proteolytic activity seems to be regulated by growth factors, endogenous inhibitors, and hormones. Studies of cathepsin D in breast cancer showed that its activity is related to estrogen action. To evaluate the relationships between cathepsin D and steroid receptor status...
The human adrenal secretes high amounts of DHEA and DHEA-S that are converted into active androgens and/or estrogens in peripheral target intracrine tissues. Type 1 3β-HSD; types I, II, III, IV, and V 17β-HSD; types I and II 5α-reductase; and aromatase are expressed specifically in individual target cells, thus regulating the local intracellular formation of sex steroids. The serum levels of DHEA...
The recently introduced transneuronal tracing technique, e.g., viral labeling of synaptically connected neurons using pseudorabies virus (Bartha's strain) was applied and injected into the ovary to reveal the spinal and supraspinal neuronal connections of the ovary. Labeled neurons were detected in the thoracic segments of the spinal cord. In the brain, virus-labeled cells were in the area postrema,...
Granulosa cells obtained from patients undergoing in vitro fertilization produce significant amounts of estradiol and progesterone. Because they cease to divide, the life span of these cells in primary cultures is limited. We established new granulosa cell lines by triple transfection of primary cells with SV40 DNA, Ha-RAS gene, and a temperature-sensitive mutant of the p53 gene (p53 Val 135). ...
We previously demonstrated that androgen receptor (AR) gene is expressed in normal and adenomatous human adrenocortical tissues and in the NCI-H295 human adrenocortical cancer cell line. Furthermore, our results indicated that androgen (dihydrotestosterone DHT) inhibits human adrenocortical cell growth in vitro at physiological concentrations. We showed a slight decrease of c-myc RNA levels in NCI-H295...
In the present work, we have inspected pathways of active cell death (ACD) in cultured human prostate tumor cells, either hormone-responsive (LNCaP) or nonresponsive (PC3). We have used immunochemical specific assay (TUNEL) to reveal 3 -OH termini of DNA fragments originated from cleavage of genomic DNA that typically occurs in ACD. DNA strand breaks were labeled by the addition of fluorescein-conjugated...
Several reports have shown an interaction between the estrogen receptor (ER) and the protein kinase C (PKC) intracellular pathways. Data from our laboratory showed that PKC activation can modulate ER levels and responsiveness in estrogen target tissues such as uterus and bone. In particular, ROS.SMER#14 osteoblastic cells, stably transfected with the mouse ER, are unresponsive to estrogenic stimulation...
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