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Ovarian steroids, estradiol and progesterone, are responsible for providing the trigger for the preovulatory surge of gonadotropin responsible for ovulation. The steroid modulation of the gonadotropin surge is exerted through excitatory and inhibitory signals from neurotransmitters that respond to the steroid signal. Among the excitatory signals, the endogenous excitatory amino acid (EAA) neurotransmitter...
5α-Reductase (5αR) 2 deficiency 46 XY pseudohermaphrodites, who are born with female or ambiguous genitalia and are largely raised as girls, often dramatically turn around toward puberty to become muscular men with small genitalia and minimal tendency for body hair growth, all probably due to deficient formation of dihydrotestosterone (DHT) from testosterone (T). These subjects, despite their gender-disordered...
The 11β-hydroxyl group is essential for glucocorticoid (GC) activity of a steroid. Thus, 11β-hydroxysteroid-dehydrogenases (HSD) are important, because they convert active GCs to their inactive 11-dehydro-products and vice versa. HSD-I is widely distributed and acts mainly as a reductase. In the liver, this isoenzyme activates orally given cortisone (E) or prednisone (Al-dehydro-E) to their 11-hydroxyderivatives...
Ovarian function is a continuous phenomenon in which the ovary has its own activity and local regulation, whereas the hypothalamo-pituitary axis controls and modulates the final steps of follicular growth and ovulation under the influence of the changing tide of ovarian signals (estradiol, progesterone, inhibins). Synchronized to follicular growth, ovulation, and corpus luteum function, the endometrium...
It is generally accepted that epididymal contractility is involved in the transport of spermatozoa, however, the specific factors that control such contractility are still unknown. Using immunocytochemistry, we demonstrated that immunoreactive endothelin-1 (ET-1) is present in the basal portion of the principal cells of the epididymis, whereas using autoradiography, we found endothelin binding sites...
Proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase-delta, is closely linked to cell replication and present during G1, S, and G2/M phases of the cell cycle. In the cascade of cyclic modulations in the endometrium, cell proliferation is followed by growth and differentiation, manifested among others by the synthesis of cell-specific proteins. To study the interrelations...
Of the nearly 200,000 women diagnosed with breast cancer each year in the United States, many will be cured by local treatment alone. However, some patients who do receive systemic hormonal or chemotherapy will benefit from such treatment, whereas others who have resistant tumors will not. Clearly, management of these patients would be optimized if clinicians could accurately predict which patients...
The existence of immune-neuroendocrine interactions is well established. Special attention has been devoted to cytokine modulation of endocrine and metabolic functions. Very little is known about the modulatory role of interleukins (IL) upon glucocorticoid receptor (GR) number and/or affinity. Glucocorticoids are well-recognized modulators of immunocytes and osteoblasts via specific receptor-mediated...
Granulosa cells plays a crucial role in follicular development and in the formation of the corpus luteum and in its function. There is a growing body of evidence that in addition to endocrine, paracrine, and autocrine regulation of granulosa cell growth and differentiation, proto-oncogenes play an important role in the regulation of these processes. In each reproductive cycle, only a few follicles...
Androgen action in prostatic tissue may be mediated by growth factors such insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma/epithelium interaction. IGF-binding proteins (IGFBPs) have a role as autocrine and/or paracrine factors in regulating the local actions of the IGFs. In this study, testosterone (T), dihydrotestosterone (DHT),...
Glutamate is an important excitatory signal in the hypothalamus for the steroid-mediated preovulatory gonadotropin surge. Steroids could exert this action by regulating glutamate receptor levels or glutamate release or both. Our previous work showed that no changes occurred in NMDA and kainate receptor binding in the hypothalamus of castrated or castrated + steroid-replaced male and female rats...
We have inspected pathways of 17β-oxidation of either androgen or estrogen in human prostate cancer cells (LNCaP, DU145, and PC3) in relation to the expression of mRNAs for 17β-HSD types 1 to 4. High expression levels of 17β-HSD4 were consistently observed in all three cell lines, whereas even greater amounts of 17βHSD2 mRNA were detected solely in PC3 cells. Neither 17β-HSD1 nor 17β-HSD3 mRNAs could...
In order to study lipid synthesis in female hamster flank organs during the estrous cycle, glands were obtained from different animals during different phases of the cycle. Lipid metabolism of [U- 14 C]glucose was studied under in vitro conditions. The radioactive lipids formed, were extracted from the glands and quantified. An aliquot of the extract was submitted to TLC to isolate...
In this paper, we studied the effect of heme availability on corticosterone and aldosterone synthesis in rat adrenal. We found that hemin stimulated corticosterone and aldosterone production in adrenal homogenates in a dose-dependent fashion. Hemin administration to rats also provoked an increase in both corticosterone and aldosterone content in adrenal. 3,5-Diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine...
Alkylation of 3,17β-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17β-bis(2-trimethylsilyl)ethoxymethyl-7-α-(4 -pentenyl)-1,3,5(10)estrat riene-6-one (3) in excellent stereoselectivity (>95% epimeric excess). Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to...
The preparation and characterization of the Fab and F(ab ) 2 fragments of a murine monoclonal antibody specific for aromatase cytochrome P-450 and which is suppressive of estrogen biosynthesis are described. This monoclonal antibody, MAb3-2C2, was purified from murine ascites using protein A affinity chromatography and digested with immobilized papain to produce antibody fragments. The...
16α-Fluoro-17β-, 16α-fluoro-17α-, and 16β-fluoro-17β-[6,7- 3 H]estradiol were prepared from [6,7- 3 H]estrone via fluorination of 3,17-bis(tert-butyldimethylsilyloxy)-[6,7- 3 H]estratetraene with N-fluoropyridinium triflate and reduction of 16α/β-fluoro[6,7- 3 H]estrone with NaBH 4 . The three isomers were separated by silica-phase high-performance liquid chromatography...
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