Study Of Steroidogenesis Research Articles

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer.

The active vitamin D hormone, 1,25-dihydroxyvitamin D3 , exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25-dihydroxyvitamin D3 affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25-dihydroxyvitamin D3 stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes. However, in astrocytes, 1,25-dihydroxyvitamin D3 suppresses 3β-hydroxysteroid dehydrogenase and steroid 17-hydroxylase/lyase. Other studies indicate cross-talk between vitamin D signalling and signalling of oestrogens, progesterone or glucocorticoids. Reported data indicate synergistic effects of combinations of 1,25-dihydroxyvitamin D3 and other steroid hormones on neuroinflammation, neurite outgrowth and neuroprotection. Also, dysregulation of steroid pathways affecting brain cells is found in vitamin D deficiency. Thus, several studies suggest that active vitamin D may affect steroid hormone synthesis and/or signalling in the nervous system, although the potential mechanisms for these responses remain unclear. 1,25-Dihydroxyvitamin D3 suppresses proliferation in several cell types and is therefore of interest in cancer treatment. Also, epidemiological studies associate vitamin D levels with cancer risk or outcomes. Reported data on tumours of the nervous system are mainly on glioma, a common type of brain cancer. Expression of the vitamin D receptor in glioma tumours is associated with improved survival. Several studies show that 1,25-dihydroxyvitamin D3 and vitamin D analogues (synthetic vitamin D-like compounds) suppress proliferation and migration in human vitamin D receptor-expressing glioma cell lines. Studies on mechanisms for actions of 1,25-dihydroxyvitamin D3 or its analogues indicate regulation of cell cycle proteins and senescence markers. These compounds also show synergism in combination with other cancer therapies treating glioma. From the data available, vitamin D analogues emerge as interesting candidates for the future improved treatment of human glioma and possibly also other cancers of the nervous system.

Steroidogenesis: Unanswered Questions

Until the mid-1980s studies of steroidogenesis largely depended on identifying steroid structures and measuring steroid concentrations in body fluids. The molecular biology revolution radically revolutionized studies of steroidogenesis with the cloning of known steroidogenic enzymes, by identifying novel factors, and delineating the genetic basis of known and newly discovered diseases. Unfortunately, this dramatic success has led many young research-oriented endocrinologists to regard steroidogenesis as a 'solved area'. However, many important and exciting questions remain, especially concerning the mechanisms of cholesterol delivery to the steroidogenic machinery, the biochemistry of androgen synthesis, the regulation and biological role of adrenarche, fetal adrenal development and involution, the roles of steroids made in 'extraglandular' cells, and the search for genetic disorders. This review outlines some of these questions, but this list is necessarily incomplete.

Immunohistochemical Study of Steroidogenesis, Proliferation, and Hypoxia-related Proteins in Caprine Corpora Lutea during the Estrous Cycle

The corpus luteum (CL) is a transient endocrine gland that produces progesterone, a product required for the establishment and maintenance of pregnancy. In the absence of pregnancy, the production of progesterone in the CL decreases and the structure itself regresses in size. The life span and function of the CL are regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. When an ovum is released from a mature follicle, angiogenesis and rapid growth of follicular cells form the CL. The purpose of the present study was to determine whether steroidogenesis, proliferation, and hypoxia-related proteins are expressed in caprine CL. The expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor la (HIF-la) were determined in caprine CL during the estrous cycle. Cytochrome P450 side chain cleavage protein did not vary significantly during the estrous cycle; however, there was an increased expression of 3β-hydroxysteroid dehydrogenase in the early and middle stages, which rapidly decreased in the late stage. The same observations were made with respect to steroidogenic acute regulatory protein. Variations in progesterone content and expression of PCNA. HIF-la, and VEGF were consistent with this result. Thus. the steroidogenic proteins, PCNA, HIF-la, and VEGF in caprine CL are dependent on the stage of the estrous cycle.

Heme oxygenase in the rat ovary: immunohistochemical localization and possible role in steroidogenesis.

The objectives of this study were to determine if heme oxygenase (HO), which catalyzes the degradation of heme and the formation of carbon monoxide (CO), is localized in the rat ovary and, if so, to determine if hemin (a substrate for HO) or chromium mesoporphyrin (CrMP, an inhibitor of HO), alter basal or gonadotropin-induced steroidogenesis. The hypothesis was that CO produced endogenously by HO suppresses steroid hormone production by the ovary similar to the action of nitric oxide. For the histological localization of HO, sections of ovaries obtained from mature Holtzman Sprague-Dawley rats were immunostained for two of the HO isoforms, HO-1 and HO-2. Theca cells and granulosa cells of follicles and luteal cells stained for HO-1, whereas the ovarian stroma showed a low intensity of staining. Theca, granulosa cells, and corpora lutea as well as the ovarian stroma exhibited HO-2 staining. HO-2 immunostaining appeared more intense for theca cells than granulosa cells. In the study of steroidogenesis, three daily injections of hemin stimulated basal- and gonadotropin-induced androstenedione and estradiol secretion from ovaries of pregnant mare serum gonadotropin-treated immature rats in vitro, but had no effect on progesterone production. A similar treatment with CrMP suppressed basal- and gonadotropin-induced secretion of progesterone and androstenedione, but had no effect on estradiol production. These data, taken together, show the existence of HO in the rat ovary and suggest a possible stimulatory role of endogenous CO in the production of ovarian steroids.

Research Note: Antibiotic-Associated Inhibition of Steroidogenesis During Short-Term Culture of Ovarian Tissues of the Domestic Fowl

The effects of antibiotics on bovine luteinizing hormone (bLH)-stimulated output of androstenedione were examined in intact small white follicles (SWF, n = six hens), aliquots of 100,000 Fl and F2 theca cells (n = six hens), and aliquots of 10,000 Fl and F2 granulosa cells (n = eight hens). Cells and SWF were isolated from ovaries of Leghorn hens killed 20 h prior to ovulation and were incubated for 3 h in 1 mL of Medium 199 (Sigma Chemical Co., St. Louis, MO) at 37 C. Cells and follicles were incubated with 10 ng bLH and Penicillin-streptomycin (Pen-Strep; 20, 100, and 200 μ.g), gentamicin sulfate (gentamicin; 10, 50, and 100 μg), and fungizone (.5, 2.5, and 5.0 μg). Two control treatments consisted of tissues incubated alone (no bLH, no antibiotic) and tissues incubated with 10 ng bLH (no antibiotic). Androstenedione output by SWF and Fl and F2 theca cells and progesterone output by Fl and F2 granulosa cells were determined by radioimmunoassay of incubation media.The steroid contents of the incubation media were significantly increased in SWF and theca and granulosa cells with the addition of bLH. Neither Pen-Strep nor gentamicin significantly affected steroid output. Progesterone output by Fl and F2 granulosa cells was significantly reduced by the inclusion of fungizone. The inhibition of steroid output with the use of fungizone should be considered when using this antibiotic in studies of steroidogenesis in preparations of ovarian cells.

The widespread occurrence of a corticosteroid 1-alpha-hydroxylase in the interrenals of elasmobranchii.

SUMMARY A corticosteroid 1α-hydroxylase was demonstrated in interrenal tissue of eleven species of elasmobranchs by the production in vitro of 1α-hydroxycorticosterone from corticosterone, and in seven of nine species examined from endogenous precursors. Interrenal tissue was collected from the following species: the skates and rays, Raja laevis, R. clavata, R. erinacea, and Dasyatis violacea; the dogfish, Squalus acanthias and Scyliorhinus stellaris; and the sharks, Isurus oxyrinchus, Prionace glauca, Sphyrna lewini, Carcharhinus falciformis and C. obscurus. 1α-Hydroxycorticosterone was identified in interrenal incubates by determination of a constant isotope ratio (3H:14C) through chromatography and preparation of sequential derivatives. [7α-3H] 1α-Hydroxycorticosterone was biosynthesized from [7α-3H]progesterone and its identity verified by demonstration of the homogeneity of its 1-dehydrated derivative with 11β,21-dihydroxypregna-1,4-diene-3,20-dione prepared by microbial dehydrogenation of corticosterone. 14C-Labelled 1α-hydroxycorticosterone was obtained from incubations of interrenal glands as a transformation product of [4-14C]corticosterone, or by acetylation of radioinert 1α-hydroxycorticosterone with [1-14C]acetic anhydride. 11-Deoxycorticosterone and corticosterone were isolated and identified as metabolites of endogenous precursors from an interrenal incubate of P. glauca. In all species, 11-dehydrocorticosterone was noted as a metabolite in vitro of corticosterone and its identity was confirmed in an interrenal incubate of S. lewini. The results of this survey are discussed in relation to earlier studies of steroidogenesis in Elasmobranchii.