Role of growth factors in the human endometrium during aging.

The aim of this study was to investigate the possible role of epidermal growth factor (EGF) and of insulin-like growth factor-I (IGF-I) in physiological and pathological changes of the endometrial tissue during aging. Thirty-four patients undergoing hysterectomy were divided into three groups: (A) premenopausal women with regular menses, (B) pre-menopausal women with irregular bleeding and (C) post-menopausal women. Endometrial samples were collected after the removal of uterus and were used for immunohistochemical evaluation of EGF, EGF receptor (EGFr) and IGF-I and also for Northern blot analysis of IGF-I gene expression. Plasma levels of 17 beta-oestradiol (E2), D4-androstenedione (D4-A) and oestrone (E1) were also assayed. The immunohistochemical scores (HSCORES) for EGF, EGFr and IGF-I were significantly higher in groups A and B than in group C. Independently from the menstrual history, significantly higher HSCORES of EGF, EGFr and IGF-I were present in hyperplastic endometrium than in those which were proliferative and atrophic. Moreover, IGF-I mRNA expression was observed in all pre-menopausal women, whereas only 1 post-menopausal women with hyperplastic endometrium showed detectable RNA encoding for IGF-I. Higher levels of D4-A were also significantly correlated (P < 0.05) with higher HSCORES of EGF, EGFr and IGF-I. Our results suggest that the above mentioned growth factors could act as mediators of oestrogens on the endometrial functional activity.

Immunohistochemical localization of epidermal growth factor receptor in leiomyomas from women treated with goserelin depot.

Epidermal growth factor receptors (EGFr) were studied by immunohistochemistry in human myometrium and leiomyomas from women treated with the GnRH agonist (GnRH-a) goserelin. The results were compared with those obtained from women not treated. Vessel cells of leiomyomas and myometrium were always more immunoreactive than fibrocytes and myocites. In fibroids from treated patients the histochemical score (HSCORE) of vessel cells was always significantly lower (p less than 0.001) than in control patients. Our data confirm a role of EGF also in fibroid growth and suggest that, the blood supply reduction associated with the volume reduction of these tumours, consequent to the GnRH-a treatment, could be EGF mediated.

Steroid therapy and the endometrium: biological and clinical implications.

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.

The effect of L-acetylcarnitine on some reproductive functions in the oligoasthenospermic rat.

The effect of L-acetylcarnitine (LAC) on some parameters of male reproductive function was studied on rats made oligoasthenospermic with dibromochloropropane (DBCP). DBCP depresses sperm count and motility. After one injection of the drug, LAC induces a recovery of both sperm count and motility but after two injections it is ineffective. This effect is also shown visually by microscopic examination of seminiferous tubules. Among the enzymatic activities evaluated as biochemical markers of testicular function both lactate dehydrogenase and NADPH-cytochrome P 450-reductase increased significantly (P less than 0.05) after treatment with LAC in normal rats. LAC also stimulates testosterone production. It is suggested that LAC may affect testicular function.