Filter

Refine by Access

Refine by Date

—
  • Print
  • Save

Search Results

You are looking at 1 - 6 of 6 items for

  • Author: T Iguchi x
  • Refine by Access: All content x
Clear All Modify Search
Restricted access

Mouse anococcygeus muscle: sexual dimorphism and responsiveness to sex hormones

Y Fukazawa, T Iguchi, and H A Bern

Abstract

The anococcygeus muscle (AcM) is one of a pair of thin sheets of smooth muscle inserting on the rectum, having a tendinous origin largely on sacral vertebrae. The cross-sectional area of AcM in the juxtarectal region in 90-day-old male mice was significantly larger than that in females of three strains: BALB/cCrgl, ICR/Jcl and C57BL/Tw. The AcM area in female mice showed strain differences: BALB/c>ICR>C57BL. Five daily injections of testosterone into newborn ICR mice from the day of birth significantly increased the areas of AcM in both sexes at 30 days of age, but five daily injections of oestradiol-17β (OE) decreased them. The AcM area in 60-day-old ICR male mice castrated at 30 days of age was significantly smaller than in intact males, and that in ovariectomized females was significantly larger than in intact females. In both sexes, implantation of a testosterone pellet (12 mg) into gonadectomized mice on the day of gonadectomy stimulated the growth of AcM, and implantation of an OE pellet (12 mg) inhibited the growth of AcM. The AcM in both ICR and C57BL strains showed positive androgen receptor and oestrogen receptor immunostaining at 15 days. Female ICR mice exposed neonatally to diethylstilboestrol (DES) had significantly larger AcM than controls; ovariectomy at 30 days of age did not change the AcM area in 60-day-old DES-exposed mice. However, male mice exposed neonatally to DES had significantly smaller AcM than controls; castration at 30 days of age nullified this inhibition. These results suggest that both androgen and oestrogen play an important role in sexual dimorphism of the mouse AcM. Neonatal exposure to DES (but not to oestradiol) had an irreversible stimulatory effect on the AcM area in female mice.

Journal of Endocrinology (1997) 152, 229–237

DOI:
https://doi.org/10.1677/joe.0.1520229
Volume 152: Issue 2,
Pages:
229–237 (9 total)
Restricted access

Quantitative analysis of the development of genital organs from the urogenital sinus of the fetal male mouse treated prenatally with a 5α-reductase inhibitor

T. Iguchi, Y. Uesugi, N. Takasugi, and V. Petrow

ABSTRACT

The role of 5α-dihydrotestosterone (DHT) in the development of the genital organs and in the differentiation of the genital tract into prostate, coagulating gland (CG), bulbo-urethral gland (BUG) and seminal vesicle (SV) in male mice exposed prenatally to the 5α-reductase inhibitor 6-methylene-4-pregnene-3,20-dione (6-MP) has been examined quantitatively. Female ICR mice were given 7 daily s.c. injections of the inhibitor (400 mg/day) starting on day 12 of gestation and the experiment was terminated on day 19 when the fetuses were removed by Caesarian section. In the prenatally 6-MP-exposed male mice the anogenital distance was significantly shorter than in the controls. Feminization of the nipples and hypospadias of the phallic urethra were noted. Development of prostate, CG and BUG was significantly suppressed. SV and testis development were not affected. These results lend further support to the conclusion that DHT is necessary for the development of the urogenital sinus (prostate, CG and BUG) and penis, and for the regression of the nipples in male mice. Reproductive abnormalities were not found in 90-day-old mice of both sexes exposed to 6-MP in utero. The 6-MP-exposed male and female mice had a normal reproductive capacity when mated with normal mice. These results show that 6-MP-induced growth retardation of reproductive organs is evident on day 19 of gestation, but that such retardation is no longer apparent in the adult.

Journal of Endocrinology (1991) 128, 395–401

DOI:
https://doi.org/10.1677/joe.0.1280395
Volume 128: Issue 3,
Pages:
395–401 (7 total)
Free access

Epithelial c-jun and c-fos are temporally and spatially regulated by estradiol during neonatal rat oviduct differentiation

A Okada, Y Ohta, SL Brody, and T Iguchi

Expression of transcription factors binding to the activating protein-1 (AP-1) site is induced by estrogens in association with epithelial proliferation in the uterus, but, in the oviduct, the relationship between cell proliferation and differentiation and AP-1 transcription factors is not well understood. In the developing rat oviduct, we found that proliferation and differentiation of epithelial cells were region-dependently regulated by 17beta-estradiol (E2). To determine the role of AP-1 transcription factors in the development of rat oviduct, we performed immunohistochemistry for epithelial c-jun and c-fos proteins in E2-untreated and -treated newborn rats. E2 increased the expression of c-jun and c-fos during proliferation of undifferentiated epithelial cells, but diminished both proteins during accelerated differentiation of ciliated epithelial cells. A pure estrogen receptor (ER) antagonist, ICI 182,780, inhibited changes in their expression during both cell proliferation and differentiation. Importantly, no reduction of c-jun was noted in the epithelial cells of the foxj1-deficient oviduct, which lacks cilia development. This study shows that c-jun and c-fos are regulated during epithelial cell proliferation and differentiation in a region-specific manner. This provides critical information for understanding the molecular and cellular mechanisms of the development of the neonatal oviduct.

DOI:
https://doi.org/10.1677/joe.0.1820219
Volume 182: Issue 2,
Pages:
219–227 (9 total)
Free access

Effect of diethylstilbestrol on cell proliferation and expression of epidermal growth factor in the developing female rat reproductive tract

A Okada, T Sato, Y Ohta, DL Buchanan, and T Iguchi

To evaluate mechanisms of cell proliferation in the fetal female rat reproductive tract, diethylstilbestrol (DES) effects on cell division and estrogen receptor (ER), epidermal growth factor (EGF) and EGF receptor (EGF-R) expressions were determined from gestational day (GD) 15.5 to 21.5. Reproductive tracts were evaluated within three regions along the Mullerian duct axis; these were proximal, middle and caudal, which differentiate into oviduct, uterus and upper vagina respectively. In fetuses from non-treated dams, epithelial and mesenchymal proliferation, as evaluated by 5-bromo-2'-deoxyuridine incorporation, was decreased with development in all regions of the Mullerian duct. EGF levels were determined by immunohistochemistry. Mullerian epithelial EGF immunoreactivity was intense in the proximal and middle regions on GDs 15.5 and 17.5. EGF staining remained intense only in the proximal epithelia by GD 19.5 and was weak in the caudal epithelium, but substantially reduced throughout epithelia in all regions by GD 21.5. Thus, decreased cell proliferation correlated with decreased EGF expression in the developing Mullerian duct. DES (100 microg/kg body weight) was injected from GD 15 to 19 and female fetuses were collected on GD 19.5. DES increased Mullerian duct cell proliferation in the proximal epithelium and mesenchyme but decreased it in the caudal epithelium compared with oil-treated controls. No proliferative DES effect was observed in any cell type in the middle region. Mullerian duct EGF immunoreactivity was suppressed by DES compared with oil. Competitive RT-PCR indicated DES also decreased mRNAs for EGF, ERbeta1 and ERbeta2, but not ERalpha and EGF-R. These results indicate EGF may be an important regulatory factor of Mullerian duct cell proliferation, and that DES may alter cell proliferation by disrupting normal EGF, ERbeta1 and ERbeta2 expression in the developing female rat reproductive tract.

DOI:
https://doi.org/10.1677/joe.0.1700539
Volume 170: Issue 3,
Pages:
539–554 (16 total)
Restricted access

Regulation of insulin-like growth factor-binding protein-4 protease activity by estrogen and parathyroid hormone in SaOS-2 cells: implications for the pathogenesis of postmenopausal osteoporosis

Y Kudo, M Iwashita, S Itatsu, T Iguchi, and Y Takeda

Abstract

The cellular mechanisms involved in the accelerated bone loss occurring in association with estrogen deprivation as seen following the menopause are not fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of osteoblasts and one of its binding proteins, insulin-like growth factor-binding protein-4 (IGFBP-4), binds to IGF-I and suppresses biological activity. Previous studies have shown that the binding activity of IGFBP-4 in the conditioned medium of parathyroid hormone (PTH)-treated SaOS-2 osteoblastic-like cells is enhanced twofold and that this PTH-enhanced IGFBP-4 binding activity is abolished by 17β-estradiol. Levels of IGFBP-4 in the conditioned medium have been reported to be regulated not only at the level of production but also at the level of degradation which is catalyzed by a protease that specifically cleaves IGFBP-4. We have, therefore, studied the effects of 17β-estradiol and PTH on IGFBP-4 protease activity using SaOS-2 cells. SaOS-2 cells produce a protease that specifically cleaves IGFBP-4 into two fragments of approximately 18 and 14 kilodaltons. IGFBP-4 protease activity in the conditioned medium from PTH-treated cells was suppressed, while this PTH-induced suppression of protease activity was reversed by the addition of 17β-estradiol to the cultures. IGFBP-4 proteolytic activity was stimulated by IGF-I or IGF-II added exogenously and was inhibited by EDTA or protease inhibitors. IGFBP-4 proteolyzed in the conditioned medium from cells treated with PTH and 17β-estradiol was less effective at inhibiting IGF-I-stimulated [3H]thymidine incorporation into DNA compared with that proteolyzed in the conditioned medium from PTH-treated cells. The simplest explanation is that 17β-estradiol suppressed the inhibitory effect of PTH on osteoblastic activity by inhibiting the PTH-induced suppression of IGFBP-4 protease activity.

Journal of Endocrinology (1996) 150, 223–229

DOI:
https://doi.org/10.1677/joe.0.1500223
Volume 150: Issue 2,
Pages:
223–229 (7 total)
Restricted access

Growth of mouse endometrial luminal epithelial cells in vitro: functional integrity of the oestrogen receptor system and failure of oestrogen to induce proliferation

F.-D. A. Uchima, M. Edery, T. Iguchi, and H. A. Bern

ABSTRACT

Normal endometrial luminal epithelial cells isolated from ovariectomized approximately 40-day-old BALB/cCrgl mice were purified by Percoll density gradient centrifugation and grown as primary cultures in collagen gel matrix and serum-free medium. Cells increased threefold in number during the 9-day culture period. Deletion of insulin, epidermal growth factor or bovine serum albumin resulted in decreased growth. Addition of any single factor to the unsupplemented medium had no effect. Relatively high levels of cytosolic oestrogen receptors and progestin receptors were demonstrable in the cultures. Addition of oestrogen did not enhance epithelial cell proliferation. On the contrary, all doses of oestrogen (180 fmol/l to 218 nmol/l) were inhibitory. Continuous exposure to oestradiol-17β (1·8 nmol/l) for 9 days in serum-free medium resulted in a decrease in cytosolic oestrogen receptors with an associated nuclear accumulation of oestrogen receptors. A corresponding increase in cytosolic progestin receptors was also observed, indicating that no qualitative modification of the oestrogen receptor system had occurred. Thus, as previously reported for vaginal epithelial cells, oestrogen, despite its stimulation of specific product synthesis (progestin receptors), did not increase proliferation of endometrial luminal epithelial cells in this culture system.

Journal of Endocrinology (1991) 128, 115–120

DOI:
https://doi.org/10.1677/joe.0.1280115
Volume 128: Issue 1,
Pages:
115–120 (6 total)