Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 217 records · Page 12Linked to original sources

PubMed1996

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.

Adult↗

PubMed1996

K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient.

Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.

Adult↗

PubMed1996

Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica.

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250-500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and beta-lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, umcommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.

Adolescent↗

PubMed1996

Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium.

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.

Adult↗

PubMed1996

Adrenal 4-binding protein in common epithelial and metastatic tumors of the ovary.

Adrenal 4-binding protein (Ad4BP) is a transcription factor that regulates the expression of steroidogenic enzymes. Ovarian tumors other than sex cord stromal tumors are occasionally associated with functioning stroma or hormonal abnormalities. To determine the steroidogenic potential of these tumors, the authors determined the immunohistochemical distribution of Ad4BP in 75 patients with primary common epithelial tumors (20 cystadenomas, 15 carcinomas of low malignant potential, and 40 carcinomas), and seven patients with metastatic carcinoma of the ovary. Ad4BP immunoreactivity was observed in intratumoral stromal cells in 3 of 15 (20%) carcinomas of low malignant potential, 26 of 40 (65%) carcinomas, and three of seven (43%) metastatic carcinomas. Ad4BP immunoreactivity was not observed in the stroma of cystadenomas. Among the positive cases, Ad4BP-positive stromal cells were particularly distributed adjacent to invasive carcinomatous glands. Among ovarian carcinomas, mucinous carcinoma showed a significantly higher number of Ad4BP-positive intratumoral stromal cells than did other histological types. Results suggest that invasion of primary or metastatic carcinoma into the ovarian stroma, especially in the case of mucinous carcinoma, may render the stromal cells to acquire the potential of metabolizing and synthesizing steroid hormones.

Breast Neoplasms↗

PubMed1996

Aromatase cytochrome P450 gene expression in endometrial carcinoma.

We analysed aromatase gene expression and its regulation in seven cases of endometrioid endometrial carcinoma. Immunohistochemistry revealed the presence of strong aromatase immunoreactivity in the stromal cells of carcinoma in five out of seven cases. A polymerase chain reaction after reverse transcription (RT PCR) revealed varying levels of aromatase transcripts (0.1-27.0 amol ng(-1) total mRNA) in five cases. The alternative use of multiple exons 1 was also examined by identifying various human aromatase transcripts specific for exons 1 in RT-PCR products. Gonadal type or exon 1d was primarily used in three cases in which aromatase overexpression was not detected. The two cases in which fibroblasts type or exon 1b was used with other exons 1 as minor transcripts demonstrated aromatase overexpression in immunohistochemistry and RT PCR analysis. Further studies are required, but alternative splicing as well as use of multiple exons 1 transcripts may result in increased aromatase expression in stromal cells observed in endometrial carcinoma.

Adult↗

PubMed1996

Oestrogen producing adrenocortical adenoma: clinical, biochemical and immunohistochemical studies.

Oestrogen producing adrenocortical tumours are extremely rare. We report a 65-year-old woman who presented with abnormal vaginal bleeding, with no significant abnormalities in her uterus or ovaries, who was found to have a right adrenal mass by radiological examination. Excessive secretion of oestrogens from the tumour was demonstrated by adrenal venous sampling. Basal levels of corticosteroids were within normal limits. Adrenalectomy was performed and pathological examination revealed an adrenocortical adenoma measuring 5.5 cm in its greatest dimension, in which both clear and compact tumour cells were observed. Oestrogen levels normalized following the removal of the adrenal mass. Tissue concentrations of oestrone and oestradiol in the tumour were 6.9 (69.5 pmol/g wet tissue weight) and 34.6 (93.6 pmol/g wet tissue weight)-fold greater respectively than those of adjacent non-neoplastic adrenal cortex. Aromatase activity in the tumour tissue determined by the 3H-water method was 118.6 pmol/h/mg protein, equivalent to that of a full-term human placenta. Immunohistochemical analysis of aromatase demonstrated immunoreactivity in the tumour cells, especially in compact cells, but not in adjacent non-neoplastic adrenal cells. This is the first reported case of an oestrogen producing adrenocortical adenoma in which aromatase in the tumour cells was documented.

Adenoma↗

PubMed1996

ACTH independent Cushing's syndrome occurring in siblings.

Familial Cushing's syndrome due to ACTH independent bilateral macronodular adrenocortical hyperplasia occurring in siblings is reported. The proband was a 69-year-old woman who presented with a typical Cushingoid appearance. The serum cortisol level was elevated, with a loss of diurnal rhythm, and the plasma ACTH level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high dose dexamethasone and no stimulation by metyrapone. An abdominal CT scan showed bilateral adrenal enlargement. The patient died of a subarachnoid haemorrhage, and autopsy revealed a massively thickened adrenal cortex composed of nodules up to 3.5 cm in diameter. A pituitary adenoma was not found. We learned that the patient's elder brother was also diagnosed at 59 years of age with Cushing's syndrome due to bilateral macronodular adrenocortical hyperplasia. His plasma cortisol levels were not suppressed by high dose dexamethasone and the plasma ACTH level was undetectable. Screening of the available family members by administering 1 mg dexamethasone at midnight and performing abdominal CT scan revealed impaired suppressibility of serum cortisol associated with enlarged bilateral adrenal glands in a 64-year-old sister and a 54-year-old brother. The 64-year-old sister was considered as a possible 'affected' case in the early stages of development, because the basal level of ACTH was not suppressed and hyperplasia of the bilateral adrenal glands as revealed by CT scan was less evident.

Adrenal Cortex↗

PubMed1996

Immunolocalization of oestrogen and progesterone receptors in prostatic hyperplasia and carcinoma.

Oestrogen receptors and progesterone receptors were immunolocalized in 19 patients with benign prostatic hyperplasia and in 26 patients with prostatic carcinoma. Immunohistochemistry was performed on tissue that had been fixed in 8% paraformaldehyde and then paraffin-embedded, using microwave irradiation for antigen retrieval. Oestrogen receptor expression was observed exclusively in the stromal cells of six out of 26 (23%) patients with prostatic carcinoma, but in none of the cells of patients with benign prostatic hyperplasia. Progesterone receptor expression was detected in 16 of 19 (84%) and 17 of 19 (89%) of the epithelial cells and stromal cells of patients with benign prostatic hyperplasia, respectively. In patients with prostatic carcinoma, progesterone receptor immunoreactivity was observed in 12 of 20 (46%) and 20 of 26 (77%) of the carcinoma and stromal cells of prostatic carcinoma, respectively. The ratio of epithelial cells with progesterone receptor immunoreactivity corresponded well with that of stromal cells with immunoreactivity in patients with benign prostatic hyperplasia. However, the ratio of stromal cells with progesterone receptor immunoreactivity was much higher than that in carcinoma cells in patients with prostatic carcinoma. Immunolocalization patterns or the ratio of the cells with progesterone receptor immunoreactivity did not significantly correlate with histological differentiation or patient's age in carcinoma cases. However, patients with advanced surgical stages of disease demonstrated a significantly smaller number of carcinoma and stromal cells with progesterone immunoreactivity in patients with prostatic carcinoma. These results suggest that oestrogens do not have a direct effect on the biological behaviour of benign prostatic hyperplasia and prostatic carcinoma, but that progesterone appears to play a role in the pathogenesis of benign prostatic hyperplasia and prostatic carcinoma.

Aged↗

PubMed1996

Cytokeratin immunolocalization and lectin binding studies in oesophageal squamous dysplasia.

We examined full thickness specimens of oesophageal squamous dysplasia from both cancer-free and cancer patients using immunohistochemical labelling for cytokeratin subtypes 10/13 and 14 and for involucrin, binding studies for various lectins, and PAS/D staining before and after diastase treatment. We studied specimens from patients with oesophageal carcinoma (52 normal epithelia, and 49 with mild, 38 with moderate, and 32 with severe dysplasia), and 32 specimens from cancer-free patients (five normal epithelia and 16 with mild and 11 with moderate dysplasia). Abnormal cytokeratin expression patterns in atypical cells, i.e. both cytokeratin 10/13 and cytokeratin 14 immunoreactivity in the same cells was detected in 41 of 99 specimens with dysplasias in cancer patients. Helix aspersa, Erythrina cristagalli and Robinia pseudoacacia binding was consistently negative in atypical cells in squamous dysplasia. The non-atypical layer of squamous dysplasia, which was morphologically indistinguishable from the corresponding layer of normal oesophageal squamous epithelium, showed abnormal involucrin expression in 39/ 101 specimens, Helix aspersa binding in 74/106, diastase sensitive PAS staining in 52/110, Erythrina cristaglli binding in 28/107, and Robinia pseudoacacia binding in 16/100. There were no significant differences in the expression of these markers in dysplasia between cancer patients and cancer-free individuals with the exception of increased Robinia pseudoacacia binding in the non-atypical layer in cancer-free patients. The results indicate that abnormal patterns of cytokeratin expression and lectin binding occur not only in atypical cells but also in non-atypical cells in oesophageal squamous dysplasia.

Adult↗

PubMed1996

Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors.

Heme oxygenase is an essential enzyme in the heme catabolism that produces carbon monoxide (CO). This study was designed to examine the expression of two heme oxygenase isozyme mRNAs in the human brain and to explore the involvement of nitric oxide (NO) and various neuropeptides in the regulation of their expression. Northern blot analysis showed the expression of heme oxygenase-1 and heme oxygenase-2 mRNAs in every region of the brain examined, with the highest levels found in the frontal cortex, temporal cortex, occipital cortex, and hypothalamus. In a human glioblastoma cell line, T98G, treatment with any of three types of NO donors--sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-L-glutathione--caused a significant increase in the levels of heme oxygenase-1 mRNA but not in the levels of heme oxygenase-2 and heat-shock protein 70 mRNAs. Sodium nitroprusside increased the levels of heme oxygenase-1 protein but not the levels of heat-shock protein 70 in T98G cells. The increase in content of heme oxygenase-1 mRNA caused by sodium nitro-prusside was completely abolished by the treatment with actinomycin D. On the other hand, the levels of heme oxygenase isozyme mRNAs were not noticeably changed in T98G cells following the treatment with 8-bromo cyclic, GMP sodium nitrite, or various neuropeptides, such as calcitonin gene-related peptide, endothelin-1, and corticotropin-releasing hormone. The present study has shown the expression profiles of heme oxygenase-1 and -2 mRNAs in the human brain and the induction of heme oxygenase-1 mRNA caused by NO donors in T98G cells. These findings raise a possibility that the CO/heme oxygenase system may function in concert with the NO/NO synthase system in the brain.

Cycloheximide↗

PubMed1996

Adrenarche is associated with decreased 3 beta-hydroxysteroid dehydrogenase expression in the adrenal reticularis.

The increased production of adrenal dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) which occurs during the prepubertal period is known as adrenarche. One hypothesis for adrenarche is that alterations in intra-adrenal expression of steroidogenic enzymes within the inner reticularis zone leads to the increased production of 19-carbon steroids. We tested the hypothesis that at the time of adrenarche there is decreased expression of 3 beta HSD in the reticularis. Immunohistochemical localization of 3 beta HSD was performed and staining intensities compared between adrenal glands from children ages 4 months to 7 years (N = 11) and ages 8 to 11 years (N = 6). No difference was observed between the levels of staining in the glomerulosa and fasciculata from either age group. However, the reticularis from the older children exhibited diminished 3 beta HSD immunoreactivity. These findings suggest that as children mature there is a decreased level of 3 beta HSD in the adrenal reticularis which may contribute to the increased production of DHEA and DHEAS seen during adrenarche.

3-Hydroxysteroid Dehydrogenases↗

PubMed1996

Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome.

We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (HSD), 17alpha-hydroxylase (P450c17) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor. Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classifed the follicles morphologically according to the development of granulosa types: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3beta-HSD, P450c17, AR and Ad4BP were observed in theca cells in all seven follicles examined, but the granulosa cells were positive only for Ad4BP (4/7) and AR (7/7). These immunohistolocalization patterns resembled those in non-selected antral follicles of normally cycling human ovaries. In theca cells from types B and C follicles, follicles positive for the steroidogenic enzymes, AR and Ad4BP were decreased in number. There were no significant differences between types A and B PCO follicles in the Ki67 labelling index of granulosa or theca cells, and between PCO and antral follicles from normally cycling human ovaries. Data demonstrate that the follicles of PCO are by no means atretic and are actively involved in both steroidogenesis and cell proliferation. The absence of ER and aromatase expression in the granulosa cells of PCO may be important in abnormal follicular development in patients with PCOS.

3-Hydroxysteroid Dehydrogenases↗

PubMed1996

Basaloid-squamous carcinoma of the esophagus. A clinicopathologic, DNA ploidy, and immunohistochemical study of seven cases.

Basaloid-squamous carcinoma (BSC) of the esophagus is a rare but interesting neoplasm that occurs primarily in the upper aerodigestive tract. In this study, we reviewed 371 cases of esophageal malignancies and detected seven cases (1.9%) of BSC. The clinicopathologic features, light and electron microscopic findings, and immunohistochemical localization of various differentiation-related antigens, including cytokeratin (CK) subtypes, p53, and epidermal growth factor receptor (EGFR), were examined. DNA ploidy was also determined in an effort to characterize the biologic features of these tumors. The tumors were classified as stage I (n = 1), IIB (n = 3), III (n = 2) or IV (n = 1). Six patients had lymph node metastasis, in four the metastatic carcinoma exhibited basaloid components. Histologically, all the tumors displayed a biphasic pattern of basaloid and squamous components. The former predominated in three cases, the latter in four cases. All the tumors contained solid growth of basaloid cells with microcystic patterns and stromal hyalinosis as well as palisading of cells. Ultrastructurally, markedly replicated basement membrane was observed. Immunohistochemistry revealed staining with only CK 14 and CK 19 antibodies in the periphery of the basaloid tumor nests. These antibodies were also positive in the basal layer of normal esophagus. Diffuse immunoreactivity for EGFR was demonstrated in all the tumors. Five tumors displayed p53 nuclear immunoreactivity. All of the basaloid components demonstrated aneuploidy by DNA image cytometry. We conclude that BSC is a distinct type of esophageal carcinoma that should be differentiated from the usual types of esophageal carcinoma and may be associated with aggressive biologic behavior.

Aged↗

PubMed1996

Mutation of cytochrome P-45017 alpha gene (CYP17) in a Japanese patient previously reported as having glucocorticoid-responsive hyperaldosteronism: with a review of Japanese patients with mutations of CYP17.

A 17-yr-old female Japanese patient, who was reported in 1968 as having glucocorticoid-responsive hyperaldosteronism but was presumed to have a defect of 17 alpha-hydroxylation mainly in the adrenal glands as the etiology of her illness, was followed. The relationship between clinical manifestations and molecular abnormalities in cytochrome P-45017 alpha gene (CYP17) was also reviewed based on the literature on Japanese patients with 17 alpha-hydroxylase deficiency. She has been treated with dexamethasone, resulting in normal blood pressure and normokalemia for 28 yr. She had almost normal gonadal function with regular menstruation on her first admission. Because of sustained genital bleeding, however, she underwent total hysterectomy with an ovarian biopsy at the age of 42 yr. No follicles or corpus luteum were detected in the ovarian specimen. At the age of 45 yr, the basal levels of sex steroids were decreased, while those of gonadotropins were increased. A genetic study on CYP17 revealed a homozygous deletion of phenylalanine (Phe) codon (TTC) at either amino acid position 53 or 54 in exon 1. A review of the literature revealed 4 patients with this type of CYP17 mutation, including the present patient, out of a total of 11 young adult Japanese patients. The clinical manifestations caused by congenitally deficient gonadal function were not marked in any of these 4 patients, but were marked in 5 of the 7 patients with different mutations of CYP17. The remaining 2 female patients had irregular menstruation. The pretreatment urine/plasma values of aldosterone were variable, normal to high, in individual patients, regardless of the structural abnormalities of CYP17. The following conclusions were suggested: 1) this type of CYP17 mutation is associated with well preserved gonadal function in young adult patients, but it likely causes early reduction of gonadal function with increasing age in these patients; 2) the prevalence of this type of CYP17 mutation is quite high in Japanese patients; and 3) the pretreatment hyperaldosteronism observed in the present patient seems not to be related to the mutation of CYP17.

Adolescent↗

PubMed1996

Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma.

The in situ formation of estradiol plays an important role in the development and biological behavior of human breast cancer Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD type 1) are two principal enzymes involved in in situ estradiol production. We evaluated the expression of aromatase and 17 beta-HSD type 1 by immunohistochemistry in 41 cases of invasive breast carcinoma (19 lobular and 22 ductal). We then examined the correlation among the expression of these enzymes, estrogen (ER) and progesterone (PR) receptor status, Ki67 labeling index of carcinoma cells, age, and the clinical stage of the patients. Marked aromatase immunoreactivity was observed in stromal cells around carcinomatous glands in 32 of 41 cases (78%), and 17 beta-HSD type 1 immunoreactivity was detected in carcinoma cells in 23 of 41 cases (56%). There was a significant correlation observed between expression of 17 beta-HSD type 1 and aromatase in invasive lobular carcinoma (P = 0.0119), but not in invasive ductal carcinoma. There was an inverse correlation between aromatase and ER status in invasive ductal carcinoma (P = 0.0213), but not in invasive lobular carcinoma. No other correlations were observed among 17 beta-HSD type 1, aromatase, PR, ER, clinical stage, age, and Ki67 labeling indexes. Aromatase and 17 beta-HSD are not always expressed simultaneously in human breast carcinoma, but their simultaneous expression is more frequent in invasive lobular carcinoma than invasive ductal carcinoma. Consequently, different mechanisms may be involved in the regulation of expression of these two enzymes in human breast carcinoma.

17-Hydroxysteroid Dehydrogenases↗

PubMed1996

Cell turnover in normal cycling human ovary.

We investigated cell proliferation and apoptosis in 37 normal cycling human ovaries to determine cell turnover in the various stages of follicular and luteal development. We examined cell proliferation by immunostaining for both Ki67 and proliferative cell nuclear antigen (PCNA) and by silver staining of nucleolar organizer regions (AgNORs). Apoptosis was examined by 3'-hydroxy nick-end labeling and by immunostaining of an apoptosis-related antigen, Ley. The labeling indexes of Ki67, PCNA, and AgNORs were significantly increased in antral follicles. However, there were no significant differences in the labeling index of Ki67, PCNA, and AgNORs between dominant and nondominant follicles, including nonovulated follicles in the luteal phase. These results indicate that the transformation of granulosa cells from quiescence to active growth is important in early folliculogenesis. Immunoreactivity for Ki67 and PCNA were observed predominantly in the functioning corpus luteum, but not in the degenerating corpus luteum, indicating proliferation only during the luteal phase. Immunoreactivity for Ley and nick end-labeling reactive cells were not observed in the follicular and luteal phases, except for scattered cells in the degenerating corpus luteum. This may be because of the relatively long process of human follicular growth and atresia.

Apoptosis↗

PubMed1996

Estrogen metabolism and impaired spermatogenesis in germ cell tumors of the testis.

We evaluated spermatogenesis in 36 patients with germ cell tumors [11 with seminoma (S) and 25 with nonseminoma (NS)] in terms of sperm concentration and histological score (Johnsen's mean score) of spermatogenesis in the ipsilateral and contralateral testes. We also measured the steroid concentration in the spermatic vein of the tumor-bearing side and performed biochemical and immunohistochemical studies of aromatase activity of the tumor to investigate the mechanism of exocrine and endocrine testicular dysfunction, with particular emphasis on the role of estrogen metabolism. The sperm concentration was significantly lower in patients with S (42.9 +/- 40.7 x 10(8)/mL) and NS (17.6 +/- 20.8 x 10(6)/mL) compared to normal adult men (114.4 +/- 41.2 x 10(6) mL; P < 0.01). The histological score was lower in patients with NS than in patients with S. The histological score was highest in the contralateral testis, followed by the ipsilateral testis far from the tumor and the ipsilateral testis near the tumor in both the S and NS groups. Serum levels of estradiol and hCG were significantly elevated in both the systemic and spermatic veins of patients with NS compared to normal values, but they were within normal limits in patients with S. The histological score count in the contralateral testis was significantly and inversely correlated with the tumor weight and serum levels of hCG and estradiol. Aromatase activity examined in 9 tumors (5 S and 4 NS) and 6 ipsilateral nonneoplastic testis (3 S and 3 NS) was significantly higher in both neoplastic and nonneoplastic testes in NS patients (tumor, 5.343 +/- 4.027; nontumor, 14.647 +/- 7.688 pmol/h.pg protein) compared to S patients (tumor, 0.622 +/- 0.408; nontumor, 1.979 +/- 1.164 pmol/h.pg protein). Aromatase immunoreactivity was observed in Leydig cells of the nonneoplastic testis in both S and NS patients and in interstitial or stromal cells in 16 of 25 of NS patients and none of S patients. Our results suggest that impaired spermatogenesis in patients with testicular germ cell tumor is caused by increased tumor size in both NS and S patients and/or by increased aromatization and in situ estrogen production in Leydig cells of the nonneoplastic testis and in interstitial or stromal cells of the tumor in patients with NS.

Adolescent↗