Biomedical subjects

Y Ibuki

Publications and source records attributed to Y Ibuki.

At least 55 records · Page 3Linked to original sources

PubMed1998

Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis.

Danazol is routinely administered orally to inhibit ovulation and to treat pelvic endometriosis. However, recent evidence suggests that danazol can act directly on endometriotic tissue in vitro to inhibit DNA synthesis and induce apoptosis. Danazol was administered via the vagina in this study, using a vaginal ring drug delivery system containing 1500 mg of danazol. This therapy was effective for treatment of pelvic endometriosis, especially for deeply infiltrating endometriosis, resulting in a cure of dysmenorrhoea and tenderness in the cul-de-sac within 3 months, and of induration or nodularity in the cul-de-sac within 7 months. Moreover, conception was possible during insertion of the vaginal ring in 17 out of 31 infertile women with deeply infiltrating endometriosis, and in two out of eight infertile women with ovarian endometriotic cysts not adhering to the cul-de-sac and without deeply infiltrating endometriosis. Serum danazol concentrations, high during oral daily 400 mg danazol therapy, but undetectable during vaginal danazol ring therapy, explain why ovulation and conception could occur during insertion of the vaginal danazol ring, and why general side-effects, which are often observed during oral danazol therapy, were not observed during vaginal danazol ring therapy. Danazol seems to be absorbed through the vaginal mucosa and reaches the deeply infiltrating endometriosis via diffusion.

Absorption↗

PubMed1998

Biochemical evidence for autocrine/paracrine regulation of apoptosis in cultured uterine epithelial cells during mouse embryo implantation in vitro.

During embryo implantation, apoptosis is observed morphologically at the implantation site of endometrium. The objectives of this study were to demonstrate biochemical evidence of apoptosis and quantitative assessment of DNA fragmentation in uterine epithelial cells using a mouse implantation model, and to investigate the autocrine/paracrine regulation of apoptosis in uterine epithelial cells during blastocyst outgrowth. Blastocysts from day 4 pregnant mice were cultured on uterine epithelial cells for 96 h. Uterine epithelial cells dislodged by trophoblasts in endometrium-trophoblast unit demonstrated morphological features of apoptosis by Acridine Orange staining. Electrophoresis demonstrated DNA ladder and DNA fragmentation by enzyme-linked immunosorbent assay markedly increased after 48 h period of incubation. Apoptosis increased in an exponential way in accordance with trophoblast outgrowth. In addition, DNA fragmentation was shown in the epithelial cells by adding embryo-conditioned medium (CM) and the effect of embryo CM on apoptosis was significantly inhibited by anti-transforming growth factor (TGF)-beta antibody. Delayed outgrowth was observed after 48 h of incubation in the blastocysts cultured with anti-TGF-beta antibody. These results suggest there is autocrine/paracrine regulation of apoptosis in uterine epithelial cells at mouse embryo implantation and that TGF-beta might play an important role in the occurrence of apoptosis in the endometrium-trophoblast unit.

Acridine Orange↗

PubMed1998

Placental metastasis from maternal primitive neuroectodermal tumor.

The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.

Adult↗

PubMed1998

Chemical assay of iron in ovarian cysts: a new diagnostic method to evaluate endometriotic cysts.

CA-125 is abundantly secreted from ovarian endometriotic cysts, but is not specific to endometriosis. In order to develop a new, more specific diagnostic marker for endometriosis, the iron concentrations in various ovarian cysts were assayed. The ovarian cysts were punctured and the contents aspirated laparoscopically, laparotomically, or transvaginally. The iron concentration in the ovarian cystic fluid was assayed using a spectrophotometer after protein precipitations and chromogen treatment. The iron concentrations in ovarian cysts were 69.5+/-10.4 micromol/l in serous cystadenomas, 73.5+/-29.3 in mucinous cystadenomas, 65.4+/-12.4 in dermoid cysts, and 92.5+/-18.2 micromol/l in adenocarcinomas. On the other hand, high iron concentrations were demonstrated in endometriotic cysts (1,749.6+/-41.5 micromol/l), a lutein cyst (1,393.8), hemorrhagic corpus luteum (1,957.5) and endometrioid adenocarcinomas (1,860.9+/-157.9 micromol/l). Cytological smear tests of the contents as well as histological examination allowed differential diagnosis between endometriosis and endometrioid adenocarcinoma. In conclusion, assay of the ovarian cystic iron concentration is a useful diagnostic tool for the evaluation of ovarian endometriotic cysts.

Adult↗

PubMed1998

Expression and effect of adrenomedullin on rat granulosa cell.

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. To elucidate the regulation of AM production in the ovary, the effect of gonadotropin on the production of AM was studied in the cultured rat granulosa cells. A Northern blot analysis of the LH receptor and adrenomedullin yielded a major hybridizing band at 5.4 kb and 1.6 kb, respectively. In our culture system of rat granulosa cells, without any stimulus, the LH receptor mRNA was undetectable and the AM mRNA level was stably expressed for 6 days. FSH significantly induced LH receptor mRNA and suppressed AM mRNA for 4 days of culture and with the addition of hCG after 2 days of pretreatment with FSH, AM mRNA levels were markedly suppressed. FSH and 8-Br-cAMP significantly increase LH receptor mRNA and suppress AM mRNA in a dose-dependent manner. These data indicated that the differentiation of granulosa cells mediated by gonadotropins were associated by suppression in AM expression through a cAMP-dependent mechanism. On the other hand, AM stimulated a rapid rise in intracellular cAMP levels, which peaked within 15 min of addition, in a dose-dependent manner with a maximal response seen at 100 nM. Additionally, AM enhanced the effects of FSH, acting additionally to produce cAMP in the cells. AM may play a role in the process of granulosa cell differentiation as a local regulator through an autocrine/paracrine mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1998

Effects of growth hormone, activin, and follistatin on the development of preantral follicle from immature female mice.

The aim of this study was to investigate whether GH and insulin-like growth factor I (IGF-I) are involved in preantral folliculogenesis and, if so, to clarify the relationship between GH/IGF-I and activin/follistatin (FS) systems in immature female mice. Ovaries were obtained from 11-day-old mice, and preantral follicles, 100-105 microm in diameter, were mechanically isolated and selected for culture. Ten preantral follicles per well were cultured with different quantities and combinations of additives as follows: no additives (control), recombinant human FSH (rhFSH), IGF-I, recombinant human GH (rhGH), activin A, and recombinant human FS (rhFS). Mean diameters of the follicles were measured daily, and estradiol and immunoreactive inhibin levels in the cultured medium were assayed by RIA on day 4. rhGH showed stimulatory effects on the follicular diameter and the secretion of estradiol and immunoreactive inhibin. These effects were augmented by the presence of IGF-I and activin A. IGF-I alone did not show any stimulatory effect. The addition of rhFSH to activin A or to rhGH and activin A promoted preantral follicular growth and hormone production. On the other hand, GH- or activin-stimulated follicular growth was suppressed by rhFS in a dose-dependent manner. These results indicate that activin A and rhGH may play an important role in controlling earlier phases of follicular development during the infantile period, which is considered to be gonadotropin independent.

Activins↗

PubMed1998

Low-dose irradiation induces expression of heat shock protein 70 mRNA and thermo- and radio-resistance in myeloid leukemia cell line.

We examined the effects of in vitro low-dose irradiation on myeloid leukemia cells (M1 cells) and found that it enhanced the colony-forming ability (CFA) of M1 cells in semi-solid agar. This enhancement was inhibited by treatment with a protein synthesis inhibitor, cycloheximide and with an RNA synthesis inhibitor, actinomycin D, after irradiation. These findings suggested that low-dose irradiation induced the synthesis of some proteins which were attributed to the enhancement of CFA. Since we expected that one species of these proteins were heat shock proteins (hsps), we attempted to detect the hsp70 family by the Western blotting method and inducible hsp70 mRNA by the RT-PCR method. Low-dose irradiation induced the expression of hsp70 mRNA, whereas the enhancement of hsp70 (an inducible isoform) and hsc70 (a constitutively expressed isoform) expression could not be found. Furthermore, the M1 cells showed thermoresistance 1 h after low-dose pre-irradiation, and also showed radioresistance 4 h after irradiation. This time difference after pre-irradiation might be attributed to the different species of proteins in showing resistance to lethal stress. Therefore, some proteins other than hsp70 were believed to be concerned with the augmentation of CFA and the induction of thermo- and radio-resistance.

Animals↗

PubMed1998

The long-term effect of menopause on postmenopausal bone loss in Japanese women: results from a prospective study.

The aim of this study was to elucidate perimenopausal bone loss in relation to menstrual conditions and to investigate the long-term effect of menopause on bone loss in aged women. The rate of change in bone mineral density (BMD) was measured twice at an exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine in 176 pre- and postmenopausal healthy women 41-65 years of age. Serum follicle-stimulating hormone, intact and N-fragment osteocalcin (OC), three types of vitamin D3, parathyroid hormone (PTH), and calcitonin were also determined. Women who exercised regularly or had anatomical changes at the lumbar spine were excluded from this study. The subjects were divided into eight groups based on their menstrual status and years since menopause. Annual bone loss at the lumbar spine of premenopausal women with regular menstruation was -0.2+/-1.9% (95% confidence interval, -0.9 approximately -0.4%) and was not statistically different from zero, while that of women with irregular menstruation or at menopausal transition was -2.1+/-3.4% (-3.4 approximately -0.8%), and -3.3+/-2.3% (-5.2 approximately -0.3%), respectively, and was significantly different from zero. Serum OC levels of women at menopausal transition were significantly higher than those of women with regular menstruation, suggesting that bone loss had commenced in these women. The rate of annual change in BMD of women who were menopausal for 1-3, 4-6, 10-12, and more than 13 years was -3.1+/-4.0% (-4.7 approximately -1.5%), -1.2+/-2.6% (-2.2 approximately -0.2%), -1.0+/-3.0% (-2.3 approximately -0.3%), and -2.3+/-2.1% (-3.7 approximately -1.0%), respectively, and was significantly less than zero. But the annual bone loss of women who were menopausal for 7-9 years was -1.5+/-2.6% (-3.0 approximately -0.1%) and was not statistically significant from zero. These results indicate that postmenopausal women lose BMD in two phases. The early bone loss is rapid and commences during irregular menstruation, then is attenuated within 6 years after the onset of menopause. The second bone loss commences after the attenuation of the first bone loss. Among bone metabolic hormones, intact PTH alone showed an age-related increase and was suggested as being a causal factor of bone loss in women who were menopausal for 13 years or more.

Absorptiometry, Photon↗

PubMed1997

Down-regulation of LH/hCG receptor in rat cultured granulosa cells.

Initial experiments established the experimental conditions necessary for the induction of LH receptor mRNA down-regulation in granulosa cells isolated from diethylstilbestrol (DES)-primed immature rats. LH/hCG receptor mRNA was first induced in granulosa cells by incubating them for 24 h with FSH. Exposure of granulosa cells to a second dose of gonadotropin caused a decrease in LH/hCG receptor mRNA and binding levels after 4 h. This effect was transient, by 12 h the mRNA levels had returned to control levels, and by 24 h the mRNA levels were higher than the control. To evaluate the ability of cAMP to down-regulate the receptor, cells were exposed to 8-Br-cAMP. The pattern of sustained decrease in LH/hCG receptor mRNA levels seen with 8-Br-cAMP was similar to that with gonadotropins. The presence of activin with FSH or hCG is more effective than FSH or hCG alone in inducing LH/hCG receptor down-regulation in rat granulosa cells. The LH/hCG receptor mRNA levels decreased in a dose-dependent manner in the presence of increasing concentrations (30-100 ng/ml) of activin with FSH. These observations indicate that an increase in cAMP causes down-regulation of LH/hCG receptor mRNA and contributes to the effect of FSH and hCG, whereas basal cAMP activity is required for LH/hCG receptor mRNA expression.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

Dual coupling and down regulation of human FSH receptor in CHO cells.

The FSH receptor is a member of the family of G protein-coupled receptors that activate adenylyl cyclase. The binding of agonist to cell surface receptors leads to a reduction in the intensity of the response to continuous stimulation, a process that is usually referred to as desensitization. Although the exact mechanism is not fully understood, the molecular cloning of the FSH receptor has made it possible to study desensitization in transfected cell lines. In this experiment FSH-induced desensitization was studied using Chinese hamster ovary cells expressing a functional human FSH receptor (CHO-FSHR cells). Stimulation of the CHO-FSHR cells with 10 ng/ml human FSH resulted in a decreased sensitivity to a second FSH stimulation. This decrease in FSH-induced cAMP production was observed within 2 h, and exposure of cells to FSH for 20 h led to a 70-80 % inhibition of cAMP formation. Moreover, the desensitization effect observed in CHO cells was mimicked by forskolin and, therefore, was mediated by cAMP. Incubation of cells with 125I-FSH showed an efficient internalization of the ligand in the CHO-FSHR cells. The CHO-FSHR cells rapidly internalized approximately 30% of the receptor-associated 125I-FSH by 2 h and 50% by 4 h. The responsiveness of individual CHO-FSHR cells to FSH was studied and administration of human FSH (30 ng/ml) induced a rapid rise in cytosolic calcium, reaching a peak at 6 sec. The data that human FSH can increase intracellular calcium in cells transfected with the FSH receptor cDNA reveal the possibility for the human FSH receptor to couple to both adenylyl cyclase and phospholipase C cascades.

Animals↗

PubMed1997

Prevention of postmenopausal bone loss with minimal uterine bleeding using low dose continuous estrogen/progestin therapy: a 2-year prospective study.

OBJECTIVE: To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss. DESIGN: A 2-year, prospective, open label, randomized study. SETTING: Department of Obstetrics and Gynecology of a university hospital. PARTICIPANTS: Fifty-two postmenopausal or oophorectomized women. INTERVENTION: One of the following regimens was continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg + medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4) control. MEASUREMENTS: Lumbar spine and femoral BMD by dual energy X-ray absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH, calcitonin. A1-p, and osteocalcin. RESULTS: Of the 52 patients enrolled in this study, 49 patients completed the 1 year of therapy and 36 completed the 2- year study. The control group showed a significant decrease in lumbar BMD over the 2 years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 approximately 12.4%), 7.4% (0.60 approximately 14.2%) and 3.20% (0.61 approximately 5.84%), respectively, and were significantly higher than pretreatment values. The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA. HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA. CONCLUSIONS: Continuous hormone replacement therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding.

Bone Density↗

PubMed1997

Enhancement of NO production from resident peritoneal macrophages by in vitro gamma-irradiation and its relationship to reactive oxygen intermediates.

The functional changes in macrophages (Mphi) following exposure to a high dose (6 Gy) of gamma-rays in vitro were investigated. Resident peritoneal Mphi obtained from C57BL/6 mice were irradiated with gamma-rays (137Cs, 0.3 Gy/min). High-dose irradiation enhanced nitric oxide (NO) production from Mphi treated with interferon-gamma and their cytotoxic activity. The enhancement of NO production by irradiation was attributed to high levels of expression of the inducible nitric oxide synthase. Furthermore, the participation of reactive oxygen intermediates in NO production was examined. Nitric oxide production was not enhanced by treatment with the membrane-oxidizing agent tert-butyl hydroperoxide or the hypoxanthine/xanthine oxidase superoxide (O2.-)-generating system. On the other hand, NO production was enhanced by treatment with a low dose of hydrogen peroxide (H2O2), which can diffuse passively through the cell membrane and can be converted into hydroxyl radicals (HO.) that cause DNA breaks. In addition, treatment with low-dose actinomycin D, which induces DNA strand breaks, enhanced NO production, but hydroxyurea, which stops DNA replication without DNA strand breaks, had no such effect. These findings suggest that DNA strand breaks caused by hydroxyl radicals formed inside the cells by gamma-irradiation, or strand breaks caused directly by radiation, plays an important role in the enhancement of NO production, but peroxidation of cell membranes has little effect.

Animals↗

PubMed1997

Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women.

In order to analyze the role of the estrogen receptor (ER) gene allelic polymorphisms on bone mineral density (BMD), 173 pre- and postmenopausal women were divided into four groups according to their menstrual status (group A: premenopausal women; group B: late premenopausal women; group C: postmenopausal women who had menopause for 5 years or less; and group D: postmenopausal women who had menopause for more than 5 years), and the relationship between ER gene polymorphism and lumbar spine BMD, the percent annual change in BMD and biochemical markers were studied. The restriction fragment length polymorphism (RFLPs) were represented as Xx (XbaI) and Pp (PvuII), with upper case and lower case letters signifying the absence or presence of restriction sites, respectively. In group A, the Xx genotype had significantly higher BMD (p < 0.01) than the xx genotype, but the difference was lost in groups B, C, and D. Because the percent annual change in BMD of group A was 0.052% and was not statistically different among genotypes, it is suggested that RFLP by Xba I is closely linked with peak bone mass that was attained during the subject's late thirties. In group B, serum N-region osteocalcin (N-OC) levels and the percent annual change in BMD showed a significantly larger increase than that of group A, indicating postmenopausal bone loss had commenced. Because the N-OC level of the Xx genotype was significantly higher than that of the xx genotype (p < 0.05), and the percent annual change in BMD of the Xx genotype showed a tendency to increase (p = 0.072), it is suggested that the high BMD of the Xx genotype is rapidly lost during menopausal transition. There were no significant relationships between RFLP and BMD in groups C and D, and between RFLP and BMD in groups C and D, and between RFLP by PvuII and BMD. The present study suggests that the Xx genotype is involved in accretion of BMD during young adulthood, but the effect was lost during menstrual transition.

Adult↗

PubMed1997

Expression of follicle-stimulating hormone receptor in human ovary.

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are key hormones in the regulation of ovarian function. The acquisition of FSH receptors during folliculogenesis is believed to be a key event in the subsequent development of the follicle. However, the binding and biochemical properties of the human FSH receptor are not well-characterized owing to the low abundance of these receptors and the limited availability of human tissue. The binding experiments show that, while the affinity of the FSH receptor does not change through the menstrual cycle, the total number of FSH receptors in the leading follicles increases by about two-fold at mid-follicular phase compared with those at other periods. Northern blot analysis was used to measure relative levels of FSH receptor mRNA, and in situ hybridization was used to localize FSH receptor transcripts. Northern blot analysis of human ovaries detected two transcripts (4.1 and 2.4 kb) for the FSH receptor. The FSH receptor mRNA was abundant in the preovulatory follicle, with expression decreased by about 50% in the corpus luteum. Using in situ hybridization, FSH receptor mRNA was found to be confined to the granulosa cells of developing follicles. A reverse transcription-polymerase chain reaction amplification was used to detect the expression of different isoforms of the FSH receptor mRNA in human corpus luteum and placenta.

Adult↗

PubMed1997

Expression of luteinizing hormone/human chorionic gonadotrophin (LH/HCG) receptor mRNA in the human ovary.

The gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH) are key hormones in the regulation of ovarian function. In the present study, the expression of LH/human chorionic gonadotrophin (HCG) receptor mRNAs in the human ovary was examined. Northern blot analysis was used to measure relative amounts of LH/HCG receptor mRNA, and in-situ hybridization was used to localize LH/HCG receptor transcripts. Northern blot analysis of human ovaries detected three transcripts (5.4, 3.6 and 2.4 kb) for the LH/HCG receptor. LH/HCG receptor mRNA concentrations increased from preovulatory follicles to the corpus luteum of the midluteal phase, and decreased at the late luteal phase. Using in-situ hybridization, LH/HCG receptor mRNA was located predominantly in granulosa cells in the same follicle. Cloning of the human LH/HCG receptor cDNA previously revealed the existence of two alternative forms of the receptor differing by the presence (HLH-Ra) and absence (HLH-Rb) of 62 amino acids by exon 9. We have studied the functional significance of these receptor isoforms and have confirmed that they are generated by alternative splicing. A reverse transcription-polymerase chain reaction amplification was used to detect different isoforms of LH receptor mRNAs in ovary and placenta. The expression of the two mRNA forms of LH/HCG receptor were detected in ovary, and at very low concentrations in placenta. Treatment with HCG caused a dose-dependent increase in cAMP production with an initial response evident at approximately 1 ng/ml HCG in COS-7 cells expressing HLH-Ra. However, a complete loss of signal transduction was found in cells transfected with the truncated HLH-Rb.

Alternative Splicing↗

PubMed1997

Paradoxical action of activin A on folliculogenesis in immature and adult mice.

Activin A is a gonadal protein originally isolated from follicular fluid and is recognized as a local regulator of granulosa cell differentiation. Whether activin A promotes folliculogenesis, however, still remains unclarified. The present study was designed to elucidate the effect of activin A on follicular growth in in vitro follicle culture systems. Preantral follicles, 100-120 microm in diameter, were mechanically isolated from BDF1 hybrid immature mice (11 days old) and adult mice (8 weeks old), then cultured for 4 days in a serum-free medium supplemented with activin A (100 ng/ml), FSH (100 mIU/ml), and a combination of both. Follicular diameter was measured daily, and the amount of estradiol and inhibin released at day 4 was determined by RIA. Preantral follicles collected from immature mice showed a significant increase in diameter when cultured with activin A or both activin A and FSH. FSH alone showed no significant effect on the diameter of follicles from immature mice. In contrast, the diameter of preantral follicles from adult mice significantly increased in response to FSH. Activin A did not stimulate growth of follicles from adult mice, and more interestingly, blocked the effect of FSH. The inhibitory action of activin A was in part restored by co-culture with follistatin (100 ng/ml). These results indicate that activin A is folliculogenetic in the prepubertal mouse, but not in adults.

Activins↗

PubMed1997

Transcriptional and post-transcriptional regulation of FSH receptor in rat granulosa cells by cyclic AMP and activin.

The effect of FSH on the induction of FSH receptors in granulosa cells is believed to be mediated, at least in part, by the cAMP second messenger system. We examined the effect of activin and cAMP on FSH receptor expression in this culture system. Steady-state levels of FSH receptor mRNA, analyzed by Northern blot hybridization, increased 3.5-fold in response to 24-h incubation with activin and 1.7-fold with 12-h incubation with 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP; 0.2 mM). We have investigated whether 8-Br-cAMP- and/or activin-induced increases in FSH receptor mRNA levels are the result of increased transcription and/or altered mRNA stability. The rates of FSH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, increased 3-fold in cells treated with activin and 1.5-fold in cells treated with 8-Br-cAMP for 2 h. To examine the degradation rates of FSH receptor mRNA transcripts, granulosa cells were preincubated with 8-Br-cAMP, activin, or medium alone for 6 h. After the preincubation period, 5 microM actinomycin-D or 200 microM 5,6-dichloro-1-beta-ribofuranosyl benzimidazole were added to arrest new RNA synthesis. The decay curves for the 2.4 kb FSH receptor mRNA transcript in granulosa cells were not significantly different in the absence or presence of 8-Br-cAMP. Activin, on the other hand, significantly altered the slope of the FSH receptor mRNA decay curve and increased the half-life of the 2.4 kb FSH receptor mRNA transcript. These data provide evidence that cAMP induces FSH receptor mRNA levels by stimulating the transcription rate and that activin increases FSH receptor mRNA levels both by stimulating transcription rates and by stabilizing the FSH receptor mRNA transcripts.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

[Mechanism on onset of secondary sexual characteristics in the female].

Adrenal androgens begin to increase approximately 2 years before the increase in gonadotropin secretion. This contributes to the growth of pubic hair. The development of the breast is primarily under the control of estrogens by the ovary. Reactivation of hypothalamic LHRH pulse generator is the most important in the onset of puberty. This reactivation initially occurs during sleep, followed by sleep-associated LH release and the increase of estradiol during daytime hours. Thereafter, the secretion of gonadotropin and estradiol increases through puberty and the positive action of estradiol on gonadotropin release is established in the middle to late puberty. Recently, growth hormone has been suggested to excert direct ovarian actions and may be involved in onset of secondary sexual characteristics.

Animals↗