Shigeo Igarashi

Cloning and sequencing of a rat type II activin receptor

A full‐length cDNA for a rat type II activin receptor was cloned by hybridization from a rat ovary cDNA library. The deduced amino acid sequence (513 residues) containing a single membrane‐spanning domain and an intracellular kinase domain with predicted serine/threonine specificity. The amino acid sequence is 99.8% and 99.4% identical in the coding region with the previously cloned mouse and human type II activin receptor, and only 66.7% identical in the coding region with the previously cloned rat type IIB activin receptor. We examined the effect of PMSG‐hCG on the mRNA level of type II activin receptor in immature rat ovaries. Northern blot analysis of ovarian RNA revealed two mRNAs (3.0 kb and 6.0 kb).

Regulation of Follicle-Stimulating Hormone Receptor

The acquisition of follicle-stimulating hormone (FSH) receptors during folliculogenesis is believed to be a key event in follicle development. We have examined the effects of FSH and activin on FSH receptor mRNA in cultured rat granulosa cells. Treatment of granulosa cells with FSH resulted in transient suppression of the FSH receptor mRNA levels 2-6 h after treatment, with subsequent recovery at 24 h. We could not detect a similar effect on FSH receptor mRNA by 8-bromoadenosine 3,5-cyclic monophosphate, which continuously stimulated FSH receptor mRNA over a similar time course. On the other hand, stimulation of the protein kinase C (PKC) pathway with phorbol myristate acetate mimicked the time course of the effects of FSH on the levels of FSH receptor mRNA. Taken together, these results suggest that the cAMP cascade may increase the mRNA levels of FSH receptor and, at the same time, the other cascade, PKC, may decrease FSH receptor mRNA levels. To further investigate the role of activin in the regulation of granulosa cell function, we studied the effect of activin on FSH receptor mRNA levels. Compared to the control, treatment with activin (100 ng/ml) increased FSH receptor mRNA in a time-dependent manner with a maximum circa 4-fold increase at 24 h. Treatment of granulosa cells with activin (20-300 ng/ml) for 24 h increased FSH receptor mRNA in a dose-dependent manner to a maximum circa 4-fold increase at concentrations of 100-300 ng/ml. Although follistatin alone had no detectable effect on FSH receptor mRNA levels, combination of follistatin (0-200 ng/ml) with activin (100 ng/ml) caused a significant reduction in the levels of activin-induced FSH receptor mRNA in a dose-dependent manner.

Primary hypothyroidism presenting as multiple ovarian cysts in an adult woman: A case report

A 21-year-old woman was referred because of abdominal pain. On physical examination, her abdomen was distended up to the umbilical region. Ultrasound and computer tomography of the abdomen revealed bilateral multiple ovarian cysts. Laboratory studies revealed increased liver function, total cholesterol and creatine phosphokinase. Further clinical investigations determined that the patient suffered from primary hypothyroidism due to autoimmune thyroiditis. The cysts resolved spontaneously after the simple replacement of a thyroid hormone. Some reports have been published of primary hypothyroidism presenting as ovarian cysts and precocious puberty in prepubertal girls. However, the case presented herein indicates that an ovarian tumor as a result of hypothyroidism may also occur in adult females. To avoid inadvertent surgery to remove an ovarian tumor, it is essential that a patient with multiple ovarian cysts and hypothyroidism be properly managed, as the simple replacement of a thyroid hormone could resolve the ovarian cysts.

Developmental changes of testicular activin and FSH receptor mRNA and plasma FSH and inhibin levels in the rat

To investigate the changes in the FSH receptor and the activin receptor during sexual maturation in rat testes, we examined the mRNA levels of the receptors by Northern blot analysis. With a full length rat activin receptor cRNA probe in this study, Northern blot analysis revealed two activin receptor mRNAs (6Kb and 3Kb) in testes. The large messenger (6Kb) was low on day 7, and gradually increased by day 35. On the other hand, the small messenger (3Kb) was low on day 7, began to increase on day 21, and had increased dramatically by day 35. Therefore, compared with our previous data, developmental changes in the mRNA of the activin receptor of male and female gonads showed certain differences. The expression of 3Kb activin receptor mRNA in rat testis may be relevant to the stimulated spermatogenesis in this period. 2.4Kb and 5.5Kb FSH receptor mRNA were revealed on day 7 and decreased to 80% on day 14 and remained at the same level. The Scatchard plots of FSH binding data showed that the binding affinities of testicular FSH were constant at each stage of development. Changes in the mRNA level in FSH receptor were followed by changes in the concentration of FSH receptor in testis. The rise in the plasma FSH level was concomitant with the decrease in the plasma inhibin level by day 14.

Important initiative roles of CD44 and tenascin in Sampson’s theory of the pathogenesis and development of endometriosis

Background Among several theories explaining the pathogenesis of endometriosis, Sampsons theory seems to be the most reliable and popular. However, this theory does have some problems. First, the onset of endometriosis is not as common as retrograde menstruation. Second, the surface of the peritoneum is capable of preventing the adhesion of foreign bodies such as endometrial cells. Regarding the first problem, several studies on immunosurveillance have been reported. The second problems has not yet been clarified, Therefore we investigated the problem in the present report. Methods Levels of CD44 and tenascin in both menstrual and peripheral blood were assayed in 19 healthy volunteer women in the first experiment. In the second experiment, the effects of tenascin on the activity of MMP-9 were investigated, because the invasive ability of endometriotic cells is known to be due to MMP activity. Results CD44 and tenascin concentrations were significantly higher in menstrual blood than in peripheral blood. Since CD44 is a specific hyaluronic acid receptor, CD44 in menstrual blood was demonstrated to be a specific matchmaker of adhesion between the endometrial cells and the peritoneal surface. Tenascin in menstrual blood and endometriotic cells up-regulated MMP activity and promoted the invasive action of endometriotic cells. Conclusion The present study clarified that adhesion of endometrial cells in menstrual blood on adhesion-preventive peritoneal surface was achieved by a mediator, CD44, in menstrual blood and that the ability of endometriotic cells to invade, induced by MMP, was achieved through up-regulation of MMP activity by the mediator tenascin.