Biomedical subjects

Y Ibuki

Publications and source records attributed to Y Ibuki.

At least 37 records · Page 2Linked to original sources

PubMed2000

Enhancement of O2- production from resident peritoneal macrophages by low-dose in vivo gamma-irradiation.

Superoxide anion (O2-) production after very low-dose in vivo irradiation (4 cGy) was examined in resident peritoneal macrophages. The level of production rapidly increased following treatment with the PKC activator, phorbol 12-myristate 13-acetate (PMA), but no further enhancement by low-dose in vivo irradiation was observed. On the other hand, treatment with zymosan A gradually induced O2- production, which was further increased in low-dose in vivo irradiated macrophages. The amounts of phagocytosis of zymosan A were not changed by in vivo irradiation. This indicated that the enhancement of O2- production was not due to an increase in phagocytotic activity by low-dose in vivo irradiation. Our results show that low-dose in vivo irradiation induces production of reactive oxygen species by macrophages, not only nitric oxide as reported in our previous paper but also O2-. This may contribute to the increase of cytolytic activity of macrophages after low-dose in vivo irradiation.

Animals↗

PubMed2000

Mutation analysis of the Smad6 and Smad7 gene in human ovarian cancers.

The Smad6 and Smad7 genes are members of the Smad family, involved in the transforming growth factor-beta (TGF-beta) signaling pathway. Mutations in TGF-beta receptors and their cytoplasmic elements of transduction signals commonly accompany various cancers. Using PCR-SSCP analysis we searched for the presence of Smad6 and Smad7 gene mutations in 30 human ovarian cancers and 4 ovarian cancer cell lines, and found that 12 cases (35.3%) had a polymorphism in intron 2 of the Smad6 gene and that 8 cases (23.5%) had a polymorphism at codon 208 in the Smad7 gene. Because these polymorphisms were not accompanied by amino acid substitution, the present results show that the mutations in the Smad6 and Smad7 genes are unlikely to be involved in human ovarian cancers.

Adenocarcinoma, Clear Cell↗

PubMed2000

Expression of gonadotropin and activin receptor messenger ribonucleic acid in human ovarian epithelial neoplasms.

Activin receptors (ActRs) and gonadotropin receptor mRNA expression were investigated in 18 human ovarian epithelial neoplasms. Northern blot analysis showed the presence of 3.0-kb type Ia ActR, 6.0- and 3.0-kb type IIa ActR, and 5.0-kb type IIb ActR mRNA transcripts in total RNA prepared from the cancer tissues. One carcinoma showed two major transcripts of a follicle-stimulating hormone receptor (FSH-R) gene, 4.1 and 2.4 kb, whereas the other two carcinomas showed two major transcripts of the luteinizing hormone/human chorionic gonadotropin receptor (LH-R) gene, 5.4 and 2.4 kb. These results were further analyzed by studying the corresponding PCR-amplified FSH and LH-R cDNA obtained by reverse transcription of total RNA. Expression of FSH-R mRNA was confirmed in about half of the cancer tissues. The size of the FSH-R reverse transcription-PCR product was the same as in normal ovarian follicles. Similarly, expression of LH-R mRNA was also detected in about half of the cancers. Normal ovaries and cancer tissues were homogenized, and activin concentrations were measured in extracts. Activin levels in normal ovarian tissue were around 0.59 +/- 0.01 ng/mg protein (mean +/- SE; n = 5), and activin production was detected in every cancer tissue, except one--serous adenocarcinoma. The findings in this study demonstrated that activin and ActRs are present in and synthesized by human ovarian epithelial neoplasms. Thus, activin seems to be available as an autocrine/paracrine factor in epithelial neoplasms and may contribute to the expression of FSH-R, although the roles of activin and gonadotropin in tumorigenesis has yet to be defined.

Activin Receptors↗

PubMed1999

Control of the expression of luteinizing hormone receptor by local factors in rat granulosa cells.

To identify the mechanisms underlying the hormone-dependent induction and maintenance of luteinizing hormone receptor (LH-R) in rat granulosa cells, the effect of follicle-stimulating hormone (FSH) and local factors on the LH-R mRNA levels were studied. LH-R mRNA levels of the cells incubated with FSH decreased rapidly after medium removal, and readdition of FSH with the fresh medium did not restore these levels. On the other hand, 8-bromoadenosine 3,5-cyclic monophosphate significantly enhanced the expression of LH-R mRNA after medium removal, while the level of LH-R mRNA was lower than that of the cells replaced by original medium including FSH. In addition, the incubation with 8-Br-cAMP produced dose-dependent responses for LH-R mRNAs and enhanced the activity of 1379 bp of the LH-R 5'-flanking region, while the level of LH-R mRNA decreased 3 days after medium removal. Further studies were undertaken to assess the role of factors in maintaining the LH receptor once induced by FSH. Since FSH and cAMP increase follistatin production in granulosa cells, we examined the effect of follistatin on LH-R induction in the presence of activin and FSH. Activin induced LH-R in the presence of FSH significantly, and follistatin antagonized this effect in a dose-dependent manner. However, insulinlike growth factor-I (IGF-I) induced LH-R mRNA in the presence of FSH even after medium change. IGF-I might be one of the important factors that act in the medium to maintain LH-R levels in granulosa cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1999

Regulation of cAMP responsive element binding modulator isoforms in cultured rat ovarian granulosa cells.

A pituitary glycoprotein hormone FSH stimulates ovarian granulosa cells to induce ovarian follicular development. In this study we identified rat ovarian genes that were rapidly induced by FSH in the cultured rat granulosa cells by means of subtraction cloning. Complementary DNA clones encoding cAMP responsive element binding modulator (CREM) were identified as one of the FSH inducible genes. Northern blotting and reverse transcription and polymerase chain reaction (RT-PCR) analyses revealed that only the repressor type of CREM gene products, ICER (inducible cAMP early repressor) isoforms, were induced by FSH treatment in cultured rat granulosa cells. The induction of ICER by FSH was mimicked by reagents known to increase intracellular cAMP levels, indicating that the induction is through cAMP and protein kinase A signal transduction system. Induction of ICER was also confirmed as the protein levels. Electrophoretic mobility shift assay of granulosa cell extracts with a radiolabeled double stranded oligonucleotide corresponding to somatostatin cAMP responsive element also revealed that only the ICER proteins were induced by FSH treatment, whereas levels of CREM proteins were nearly constant regardless of the FSH treatment. Our present study demonstrates that FSH-induced and cAMP-mediated induction and attenuation of transcriptional responses by CREM gene products may be a key mechanistic component for the granulosa cell differentiation and proliferation.

Animals↗

PubMed1999

Expression of adrenomedullin in the endometrium of the human uterus.

OBJECTIVE: Our purpose was to determine whether adrenomedullin is present in the human uterus. METHODS: We obtained specimens from five patients with leiomyoma and four patients with endometrial adenocarcinoma who were undergoing abdominal hysterectomy. Tissue sections were stained with antibody against adrenomedullin using an avidin-biotin-peroxidase complex technique. Total RNA from normal and cancerous endometrium, myometrium, and leiomyoma was prepared and analyzed by northern blot methodology. RESULTS: Sections stained with an antibody to adrenomedullin showed prominent expression of adrenomedullin in the normal and cancerous endometrial epithelial cells. Northern blot analysis showed that normal and cancerous endometrium expressed the messenger RNA (mRNA) for adrenomedullin and that the size of the mRNA transcript was 1.6 kilobases (kb). No significant difference was observed between the abundance of mRNA in normal and cancerous endometrium. CONCLUSION: The findings in this study demonstrated that both adrenomedullin protein and mRNA are present in normal and carcinomatous endometrium of the human uterus.

Adrenomedullin↗

PubMed1999

Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole.

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.

Adult↗

PubMed1999

Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage.

The purpose of the present study was to investigate 1) whether activin A can cause primary follicles to become dormant at the resting stage, and 2) the role of the secondary follicle on follicular growth of primary follicles. Preantral follicles (100-120 microm in diameter) harvested from adult mice and cultured in in vitro follicle culture system showed a significant increase in size and estrogen and inhibin secretion in response to FSH, but the administration of activin A blocked the effect of FSH. Withdrawal of activin A not only restored the follicular response to FSH but also enhanced the effect of FSH, indicating that the action of activin A is to cause small preantral follicles to become dormant at the preantral stage. To investigate the role of secondary follicles in early folliculogenesis, small preantral follicles were cocultured with secondary follicle (300-350 microm in diameter) in the presence of FSH. The secondary follicle showed a significant increase in follicular diameter as a result of stimulation by FSH, but the small preantral follicles did not increase in size. After removal of the secondary follicle, however, the small preantral follicles commenced follicular growth, indicating that the growth of small preantral follicles is suppressed by the secondary follicle. Administration of the activin binding protein follistatin caused a significant increase in follicular diameter of both small preantral and secondary follicles as a result of stimulation by FSH. These results have suggested that secondary follicles cause primary follicles to become dormant at the resting stage by secreting activin.

Activins↗

PubMed1999

A role of insulin-like growth factor I in luteinizing hormone receptor expression in granulosa cells.

The present study was undertaken to identify the mechanisms underlying the effect of insulin-like growth factor (IGF-I) on LH receptor in rat granulosa cells. Treatment with FSH, as expected, produced a substantial increase in LH receptor messenger RNA (mRNA) level, and concurrent treatment with increasing concentrations of IGF-I brought about dose-dependent increases in FSH-induced LH receptor mRNA, with a maximal response 2.5-fold greater than that induced by FSH alone. IGF-I, either alone or in combination with FSH, did not affect intracellular cAMP levels, whereas it enhanced the effect of 8-bromo-cAMP on LH receptor mRNA production. We then investigated whether the effects of IGF-I and FSH on LH receptor mRNA levels are the results of increased transcription and/or altered mRNA stability. To determine whether the LH receptor 5'-flanking region plays a role in directing LH receptor mRNA expression, the proximal area of the LH receptor 5'-flanking regions were inserted into a transient expression vector, pGL-Basic, which contains luciferase as the reporter gene, and the resulting plasmids were transiently transfected into rat granulosa cells. Our studies show that the FSH-induced luciferase activity varied dependent upon the length of the 5'-flanking region sequence in the reporter gene. In addition, FSH (30 ng/ml) significantly enhanced the activity of 1379 bp of the LH receptor 5'-flanking region, but treatment with 10 ng/ml IGF-I alone did not significantly influence the activity of the LH receptor promoter or affect the increased promoter activity induced by FSH. The rates of LH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, were not increased by the addition of IGF-I. On the other hand, the decay curves for LH receptor mRNA transcript in primary granulosa cells showed a significant increase in the half-life after the addition of IGF-I. These data suggest a possible role for changes in LH receptor mRNA stability in the IGF-I-induced regulation of LH receptor in rat granulosa cells. This interface between circulating hormones and paracrine/autocrine systems could provide an important mechanism to amplify the effects of gonadotropic hormones at the local level.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1999

A comparative study on transforming growth factor-beta and activin A for preantral follicles from adult, immature, and diethylstilbestrol-primed immature mice.

Both transformation growth factor-beta (TGFbeta) and activin belong to the TGFbeta superfamily, and each receptor is structurally related. We have shown that the action of activin A on folliculogenesis is different in immature and adult mice, so it is of interest to study whether TGFbeta has such an action on follicular development. The effect of TGFbeta on folliculogenesis was studied in isolated preantral follicles from immature, adult, and diethylstilbestrol (DES)-primed immature mice and was compared with that of activin A. TGFbeta caused a significant increase in follicular diameter and estradiol and immunoreactive inhibin secretion in adult mice in a dose-related manner, but did not affect the size of preantral follicles from immature mice. Activin A, on the other hand, caused a significant increase in the size of follicles from immature mice, but did not change the size of preantral follicles from adult mice. TGFbeta enhanced the effect of FSH, whereas activin A completely blocked the action of FSH on preantral follicles from adult mice. Such a specific action of TGFbeta and activin A was age dependent because preantral follicles obtained from 28-day-old mice, compared with those from 11- and 56-day-old mice, showed an intermediate reaction to TGFbeta and activin A. DES pretreatment of 11- and 28-day-old mice caused an enhanced response to FSH, but this response was completely inhibited by TGFbeta. These results indicate that both TGFbeta and activin A have proliferative action and cytodifferentiative action on granulosa cells, but the action of each is age dependent and opposite in direction. In conclusion, although both TGFbeta and activin A belong to the same family, and each receptor is structurally related, both share a specific role in early folliculogenesis before and after puberty.

Activins↗

PubMed1999

Effect of prolactin on the expression of luteinizing hormone receptors during cell differentiation in cultured rat granulosa cells.

Chronic and transient hyperprolactinemia has been associated with luteal phase dysfunction. Recently, evidence has emerged to suggest that elevated PRL may exert its antigonadal effects through reducing available ovarian LH receptors. We have now examined the influences of PRL on LH receptor induction in cultured granulosa cells. Basal specific LH binding was negligible and remained unchanged in response to treatment with PRL by itself. Whereas treatment with FSH produced, as expected, a substantial increase in specific LH binding, concurrent treatment with PRL resulted in no significant change during the first 4 days of culture, followed by a significant decrease in LH binding on days 5 and 6 as well as an approximately 50% inhibition of FSH effect on day 6. Scatchard plot analysis showed that concurrent treatment with PRL resulted in inhibition of the granulosa cell LH binding capacity, whereas no difference could be detected in the binding affinity of LH to its receptor. Treatment with 8-bromo-cAMP produced a significant increase in specific LH binding; concurrent treatment with PRL (30 ng/ml) produced a significant attenuation of 8-bromo-cAMP action. In addition, treatment with FSH increased the intracellular accumulation of cAMP, and concurrent treatment with PRL did not result in inhibition of the FSH action, as assessed by the generation of intracellular cAMP. Taken together, these findings suggest that the ability of PRL to interfere with FSH action with regard to the induction of LH receptors is exerted at sites distal to those involved in cAMP generation. The effect of PRL on LH receptor messenger RNA (mRNA) levels was not significant during the increase in receptors, whereas after the maximal level of receptor expression was reached, the effect of PRL was apparent. Cotreatment with FSH (30 ng/ml) and increasing doses of PRL inhibited the levels of FSH-induced LH receptor mRNA in a dose-dependent manner, whereas PRL did not inhibit the effect of FSH on the FSH receptor mRNA. To investigate the hormonal regulation of the 5'-flanking region, we analyzed the effect of FSH on 1379 bp of LH receptor promoter in rat granulosa cells. Treatment with FSH (1-100 ng/ml) significantly enhanced the activity of 1379 bp of the LH receptor 5'-flanking region in dose-dependent manner. Treatment with 30 ng/ml PRL alone did not significantly influence the activity of the LH receptor promoter and did not affect the increased promoter activity induced by FSH. In addition, the rates of LH receptor mRNA gene transcription assessed by nuclear run-on transcription assay increased by the addition of FSH and were not affected by the addition of PRL in the presence of FSH. These data showed that PRL might not effect LH receptor gene transcription in the regulation of LH receptor mRNA. Next, an attempt was made to determine the effect of PRL on LH receptor mRNA stability by measuring the decay of LH receptor mRNA under conditions known to inhibit transcription. However, inhibitors of transcription were found to have a stabilizing effect on the LH receptor mRNA, thus potentially masking the effect of PRL. According to the expression of LH receptor mRNA, PRL might not affect the maximum level induced by FSH, but thereafter the maximum levels of LH receptor mRNA decreased faster than those of the control. Therefore, it may be possible that PRL acts to stimulate labile LH receptor mRNA-destabilizing factors.

Animals↗

PubMed1999

Contribution of inflammatory cytokine release to activation of resident peritoneal macrophages after in vivo low-dose gamma-irradiation.

The activation mechanism of resident peritoneal macrophages by in vivo gamma-irradiation was investigated. The function of macrophages as accessory cells in concanavalin A-induced proliferation of spleno-lymphocytes (accessory function) was enhanced 4 h after a low-dose irradiation (4 cGy) in vivo, but not in vitro, indicating that low-dose irradiation acts indirectly on the activation of macrophages. Because we expected that macrophages were activated by the recognition of substances damaged by in vivo irradiation, we co-cultured macrophages with oxidized erythrocyte-ghosts. No change was found in their accessory function. The production of inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), in the supernatant of cocultures of spleno-lymphocytes and macrophages was determined by an ELISA. Production of both increased in the presence of in vivo irradiated macrophages. Furthermore, IL-1 beta production from in vivo-irradiated macrophages treated with recombinant IFN-gamma also was enhanced. The mRNA expression of the cytokines released from macrophages and lymphocytes was determined by RT-PCR. Increases in IL-1 beta mRNA expression were found in both in vivo- and in vitro-irradiated macrophages. In vivo irradiation also enhanced the expression of IFN-gamma mRNA in lymphocytes, whereas there was no change after in vitro irradiation. On the basis of these observations, we propose that the activation of macrophages is caused by interaction with neighboring cells, such as lymphocytes, and by paracrine induction of certain cytokines which is initiated by the small amount of IL-1 beta released by irradiated macrophages.

Animals↗

PubMed1999

Mutation analysis of the Smad3 gene in human ovarian cancers.

The Smad3 gene is a member of the Smad family, vertebrate homologues of Drosophila Mad, and its gene product is a cytoplasmic element in the transforming growth factor-beta (TGF-beta) signaling pathway. Mutations in TGF-beta receptors and their cytoplasmic elements of transduction signals commonly accompany various cancers. Using PCR-SSCP analysis we searched for the presence of Smad3 gene mutations in 36 human ovarian cancers, and found that 15 cases (41. 7%) had a polymorphism at codon 103. Because this mutation was not accompanied by amino acid replacement, the present results show that the mutations in the Smad3 gene are unlikely to be involved in human ovarian cancers.

Adolescent↗

PubMed1998

The effect of activin and FSH on the differentiation of rat granulosa cells.

The differentiation of granulosa cells is regulated by follicle-stimulating hormone (FSH) and local ovarian factors. To further analyze the role of FSH and activin in this process, we have examined the effect of FSH and activin on FSH and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor induction in granulosa cells. Granulosa cells from diethylstilbestrol (DES)-primed immature rats produce activin and maintain FSH receptor without LH/hCG receptor expression in the absence of FSH. On the other hand, FSH induced granulosa cells to differentiate into more mature granulosa cells in which higher LH/hCG receptor expression and diminished activin production were observed.

Activins↗

PubMed1998

Determination of a normal level of serum CA125 in postmenopausal women as a tool for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

In an attempt to determine a normal level of CA125 in postmenopausal women, CA125 levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8 +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was found in postmenopausal women without HRT and was significantly lower than that of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the cutoff level of CA125 in postmenopausal women or women without reproductive organs should be estimated at a level lower than that conventionally accepted. A receiver operating characteristic (ROC) curve for a preoperative evaluation of myometrial invasion was analyzed in postmenopausal women with endometrial cancer (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial invasion to more than one-half of the myometrium with sensitivity of 69.0%, specificity of 74.1%, positive predictive value of 58.8%, and negative predictive value of 81.6%. In addition, the distribution of CA125 levels was analyzed in patients who had undergone an operation for endometrial cancer more than 2 years earlier and as yet had no clinical evidence of recurrence of the disease. Ninety-six point two percent of 619 measurement values were lower than 20 U/ml. These results suggest that the novel CA125 level of 20 U/ml is clinically useful for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

Aged↗

PubMed1998

A comparative study of fixed-dose, step-down, and low-dose step-up regimens of human menopausal gonadotropin for patients with polycystic ovary syndrome.

OBJECTIVE: To compare the efficacy and safety of the fixed-dose, the step-down, and the low-dose step-up regimens of hMG for women with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized study. SETTING: Gunma University School of Medicine, Maebashi, Japan. PATIENT(S): Thirty-seven women with PCOS. INTERVENTION(S): The fixed-dose, the step-down. and the low-dose step-up regimens were administered. MAIN OUTCOME MEASURE(S): The number of growing follicles and serum hormone levels. RESULT(S): Serum FSH levels on the day of hCG administration were significantly higher in the fixed-dose regimen group than in the step-down and the low-dose step-up regimen groups, and the number of growing follicles (> or =11 mm) in the low-dose step-up regimen group was significantly smaller than in the fixed-dose regimen group. On the 7th day after hCG administration, the maximal diameter of the ovaries in the low-dose step-up regimen group was significantly smaller than in the fixed-dose and the step-down regimen groups, and the risk of excessive ovarian enlargement (> or =70 mm) was significantly lower in the low-dose step-up regimen group than in the fixed-dose regimen group. CONCLUSION: The low-dose step-up regimen of hMG for patients with PCOS may be the safest protocol among the three stimulation regimens for reducing multiple follicular development.

Adult↗

PubMed1998

Orchiectomy and response to testosterone in the development of obesity in young Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats.

OBJECTIVE: Withdrawal of testosterone prevents the development of hyperglycaemia in male Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus (NIDDM), but the exact mechanism has not been established. The present studies were undertaken to examine a possible role of testosterone in the development of obesity in young OLETF rats who have not shown marked hyperphagia. METHODS: Body weight, food intake and circulating concentrations of metabolic factors including immunoreactive leptin (IRL) were measured at five weeks of age in young male OLETF rats and their lean controls, Long-Evans-Tokushima-Otsuka (LETO) rats. At six weeks of age, both LETO and OLETF rats were bilaterally orchiectomized (Orchx) and half of each group implanted with a silastic tube containing testosterone. After a three week observation period, all animals were killed and circulating concentrations of metabolic factors and the ob gene expression in retroperitoneal white adipose tissues were measured. RESULTS: Body weight and 24h food intake were already increased in OLETF rats at five weeks of age. Serum testosterone concentrations were significantly lower in OLETF rats than in LETO rats. Expression of the ob gene was significantly decreased in the retroperitoneal white adipose tissue of OLETF rats, and their serum IRL concentrations were lower. Food intake and body weight gain for three weeks after the operation were significantly lower in the Orchx group of OLETF rats than in the sham-operated group. Hyperglycaemia, accompanied by hyperinsulinaemia, was attenuated by orchiectomy in OLETF rats. Circulating IRL concentrations were significantly higher in OLETF rats than in LETO rats and decreased by orchiectomy. Testosterone supplement reversed all of the changes caused by orchiectomy in OLETF rats. In contrast, the changes, which were observed after orchiectomy in OLETF rats, were not obvious in LETO rats. CONCLUSION: The present data indicate that testosterone plays a role in the development of obesity and NIDDM in young OLETF rats, but that changes of leptin production in white adipose tissue may not be important in the development of obesity in young OLETF rats.

Animals↗

PubMed1998

Changes in bone mineral density after orchidectomy and hormone replacement therapy in individuals with androgen insensitivity syndrome.

Changes in bone mineral density (BMD) after orchidectomy and after hormone replacement therapy were reported in two patients with complete androgen insensitivity syndrome (AIS). Diagnosis of AIS was made by clinical features and confirmed by the presence of 46,XY karyotype and the presence of testis component in the removed gonads. BMD at the lumbar spine and at three sites of the femur was measured by dual energy X-ray absorptiometry (DXA). The Z scores of the lumbar spine BMD before orchidectomy were -0.8 and -3.1, confirming that patients with AIS have low BMD and that androgen plays an important role in bone mineralization in 46,XY individuals. Castration reduced BMD, but treatment with daily doses of 1.25 mg of conjugated oestrogen and 10 mg of medroxyprogesterone acetate increased BMD. These results indicate that both oestrogen and androgen play an important role in balancing BMD in men.

Adult↗