Biomedical subjects

M Tetsuka

Publications and source records attributed to M Tetsuka.

23 records · Page 2Linked to original sources

PubMed1997

Differential expression of messenger ribonucleic acids encoding 11beta-hydroxysteroid dehydrogenase types 1 and 2 in human granulosa cells.

In glucocorticoid target organs 11beta-hydroxysteroid dehydrogenase (11betaHSD) regulates the levels of active glucocorticoids available to glucocorticoid receptors. To date two isoforms of 11betaHSD, NADP-dependent type 1 11betaHSD (11betaHSD1) with predominant reductase activity and NAD-dependent type 2 11betaHSD (11betaHSD2) with dehydrogenase activity have been identified. Human ovarian granulosa cells have been shown to possess both dehydrogenase and reductase 11betaHSD activities and express 11betaHSD1 mRNA. However, whether 11betaHSD2 mRNA is also present or if the expression of either mRNA is developmentally regulated in the human ovary is unknown. We therefore used northern analysis to examine 11betaHSD1 and 11betaHSD2 mRNA levels in non-luteinized and luteinizing granulosa cells, corpora lutea (CL) and ovarian stroma obtained from human ovaries. Here we show that non-luteinized granulosa cells express relatively high levels of 11betaHSD2 mRNA but not 11betaHSD1. Conversely, luteinizing granulosa cells abundantly express 11betaHSD1 mRNA but not 11betaHSD2. CL also expresses 11betaHSD2 to lesser extent. Neither 11betaHSD mRNA is detectable in ovarian stroma. These results indicate that mRNAs encoding both 1lbetaHSD isozymes are present in human granulosa cells and they are developmentally--but differentially--regulated during preovulatory follicular development. The existence of developmentally regulated 11betaHSD in human granulosa cells is important new evidence that glucocorticoids, acting directly on the ovary, serve physiologically significant roles in the regulation of folliculogenesis.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1997

Differential regulation of aromatase and androgen receptor in granulosa cells.

During follicular development, androgen acts in three distinct ways. During the early stage of follicular differentiation, androgen acts as an enhancer of FSH-stimulated follicular differentiation. As follicular differentiation progresses, this effect is decreased and androgen is mainly utilized as a substrate for estrogen synthesis under increasing stimulation of FSH and LH. These two events are mediated by androgen receptor (AR) and aromatase (P450arom), respectively. In the rat and marmoset monkey, AR and P450arom are predominantly expressed in granulosa cells, and both are developmentally regulated. The expression of AR is highest in preantral/early antral follicles and gradually decreases as follicles mature, whereas expression of P450arom is increased as follicular differentiation progresses. We propose that differential regulation of these two androgen-utilizing factors contributes to the smooth transition of developing follicles from the early stage of differentiation to the fully mature ovulatory status. A failure of this transition due to improper androgen stimulation might result in follicular atresia.

Androgens↗

PubMed1996

Androgen receptor gene expression in rat granulosa cells: the role of follicle-stimulating hormone and steroid hormones.

In rat ovary, androgen receptor (AR) is predominantly expressed in granulosa cells and is developmentally regulated. However, the exact mechanism that is responsible for the regulation of AR in granulosa cells has not been elucidated. The aim of this study was to examine 1) the levels of AR messenger RNA (mRNA) expression in granulosa cells from follicles of different size and 2) the effects of FSH, 8-bromo-cAMP, androgen, and estrogen on AR mRNA levels in granulosa cells in vitro. The abundance of AR mRNA was examined by ribonuclease protection assay using 32P-labeled AR complementary RNA probe and related to that of P450aromatase (P450arom) mRNA, a well established maker of granulosa cell differentiation. In large follicles (> 400 microns in diameter), the abundance of AR mRNA was decreased to 51% of that in small follicles (< 200 microns; P < 0.01), whereas the abundance of P450arom mRNA increased to 277% (P < 0.01). In medium follicles (200-400 microns), the abundance of AR mRNA was maintained (101%), whereas the abundance of P450arom mRNA increased to 202% of that in small follicles (P < 0.05). Treatment with FSH (0-300 ng/ml) or 8-bromo-cAMP (0-4 mM) induced P450arom mRNA in the cultured granulosa cells in a dose-dependent manner; however, it did not affect the levels of AR mRNA expression. Treatment with 5 alpha-dihydrotestosterone (1 microM) resulted in a significant reduction in the abundance of AR mRNA to 67% of the control value (P < 0.05). This effect was reversed by the addition of FSH (100 ng/ml; P < 0.01). Treatment with diethylstilbestrol (1 microM), alone or in combination with FSH (100 ng/ml), did not have any significant effect, although these treatments tended to decrease the abundance of AR mRNA to 81% and 85%, respectively. Both 5 alpha-dihydrotestosterone and diethylstilbestrol dramatically enhanced the abundance of FSH-induced P450arom mRNA compared to the effect of FSH alone. These results indicate that 1) the down-regulation of AR mRNA expression takes place in granulosa cells of preovulatory follicles; 2) FSH is not directly responsible for this event; and 3) androgen down-regulates AR mRNA expression in immature granulosa cells, and this effect is reversed by FSH. We conclude that androgen and FSH jointly regulate AR mRNA expression in rat granulosa cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Developmental regulation of androgen receptor in rat ovary.

Androgen receptor (AR) distribution and developmental regulation in the rat ovary were examined by semiquantitative immunohistochemistry. Ovarian AR mRNA levels were also determined by Northern analysis of total RNA and compared with the levels of cytochrome P450aromatase (P450arom), an established marker of preovulatory follicular maturity. Hypophysectomized immature female rats were treated with recombinant human (rh)-FSH and/or rh-LH, or human menopausal gonadotrophin (HMG). AR was predominantly located in granulosa cells. There was no indication of specific AR immunoreactivity in thecal cells, but scattered stromal cells did stain positively. In control and LH-treated ovaries, only small preantral/early antral follicles were present. Granulosa cells in these follicles showed intense AR immunostaining. Treatment with FSH, FSH and LH or HMG stimulated varying degrees of preovulatory follicular development. In these follicles, the intensity of AR immunostaining progressively declined as follicular development progressed. In intact immature rats treated with FSH, the abundance of ovarian AR mRNA was significantly decreased to 35% of the control value while combined treatment of FSH and LH resulted in further down-regulation of AR mRNA expression to 17% of the control value. A decrease in the abundance of AR mRNA was accompanied by a simultaneous increase in the abundance of P450arom mRNA. Similar results were obtained in hypophysectomized immature rats treated with FSH and LH, suggesting an inverse relationship between AR mRNA expression and granulosa cell maturity. These results suggest that (1) the AR is most abundant in the granulosa cells of rat ovaries and (2) the expression of AR and its mRNA are developmentally regulated, being down-regulated during FSH-stimulated preovulatory follicular development.

Animals↗

PubMed1989

Seven-legged calf--dipygus with an extra foreleg at the pelvic region.

A male Holstein-Friesian calf with seven legs was examined macroscopically and radiographically. External features included two normal forelimbs, two normal hindlimbs (lateral hindlimbs), and two abnormal hindlimbs (medial hindlimbs) which were underdeveloped. Also, a rudimentary forelimb, which was attached to the pelvic region, was observed between both the medial hindlimbs. It consisted of an underdeveloped humerus, a duplicated ulna, several carpal bones, a partially duplicated metacarpal bone and three digits with three hoofs. This leg was connected with two sets of coxae by a irregular-shaped bone considered the vestigial vertebrae and ribs. Two penises and scrotums, three kidneys and testes were also observed. This calf is the first case of dipygus associated with pygopagus parasiticus in cattle. Based on these findings, the pathogenesis of this rare anomaly was briefly discussed from an embryological point of view.

Abnormalities, Multiple↗