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204. Role of dihydrotestosterone on 1,2,dimethylhvdrazine-induced colon carcinogenesis
Abstracts
856
between the different age groups particularly during the neonatal period and in early infancy. It is concluded that detailed knowledge of the age dependency of the normal plasma steroid pattern is a prerequisite for the understanding of pathological situations in pediatric endocrinology.
204. Role of dihydrotestusterone on 1,2,dimethylhydrazineinduced colon carcinogen&s
MEHTA.R. G.. FRISKS. C. M. and MOON, R. C., IIT Research Institute, Chicago. IL, 60616. U.S.A. Experiments were designed to study the effects of dihydrotestosterone (DHT) on the tumor incidence in 1.2.dimethylhydrazine dihydrochloride (DMH) treated BDIX male rats. Animals receiving IS mg/kg body weight of DMH. subcutaneously once a week for 20 weeks. developed adenocarcinemas in 60”,, of the cases I5 weeks following the last injection. The tumor incidence dropped to 27”,, in DMH treated gonadectemized rats. However. the incidence in DMH-treated castrated rats receiving DHT was comparable to that of intact rats. Quantitative measurement for DHT binding proteins was made on the cytosol of colons from DMH treated and control BDIX male rats. Scatchard analyses of the results showed that the colons from control animals did not have any unoccupied saturable binding sites whereas colon cytosol from DMH treated animals bound [‘HI-DHT with high affinity (Kd = 2.5 x IO-” M) and low capacity (II = 2Ofmolimg cytosol protein). DHT receptors were uniformly distributed throughout the colon. Increasing dosage of DMH beyond IS mg did not increase the number of binding sites. The results indicate that tumorigenesis of colon is hormone responsive and that the influence of sex steroid is mediated through specific carcinogen induced DHT receptors.
205. Plasma cortisol and testosterone levels in patients with idiopathic hirsutism during hypoglycemia
KO~IJAN~I~. A.. Department for Endocrinology and Metabolic Disorders. 61000 Ljubljana. Yugoslavia In 20 female patients with idiopathic hirsutism (IH). hypoglycemia was induced by means of i.v. insulin and the concentrations of plasma cortisol and testosterone were determined at 0. 30. 60. 90 and I20 min. Mean plasma cortisol levels in IH patients did not change with hypoglycemia. whilst a non-significant decrease of the mean plasma testosterone levels was observed during the test. In the control group consisting of 6 female patients with an intact hypothalamic-pituitary-adrenal axis. the mean concentration of plasma cortisol during hypoglycemia dropped at 30 min. whereafter an appropriate increase was observed. In these patients. mean concentrations of plasma testosterone increased at 30 and 60min and then dropped to the initial values. At 30 min a negative correlation between the mean plasma cortisol and testosterone levels was found in all subjects.
206 Regulation of steroid receptors in human endometrial hyperpbia
and carcinoma
VIHKO. R.. JANNE,0.. KAUPPILA.A.. KONTULA.K. and SYRJ~L~. P., Departments of Clinical Chemistry. Bio-
chemistry and Obstetrics and Gynecology. University of Oulu. SF-90220 Oulu 22. Finland Progestin treatment has been shown to be an effective form of therapy in about one-third of patients with advanced endometrial cancer. Regression of the tumor is probably due to a localized hormone effect on the tumor cells rather than a systemically mediated action. The purpose of this study was to investigate estrogen (ER) and progestin (PR)
receptors in hyperplastic and carcinomatous endometrium and to monitor the effects of progestin administration on their concentrations. Samples were obtained by curettage before and after 2-4 weeks of progestin treatment. Cytosolit unoccupied ER and cytosolic total PR were quantified by the method of Scatchard. The mean concentrations (fmol/mg cytosol protein) of ER were 137 and 161 and of PR 822 and 687 in the proliferative (n = 14) and secretory (n = 17) endometrium. respectively. In cystic glandular (n = 14) and adenomatous (n = 4) hyperplasia the concentrations were higher (ER 186 and 294: PR 1500 and 1423. respectively). whereas in endometrial carcinoma (it = 29) the PR level was lower (366) and ER was 190. Progestin administration led IO a decrease in ER and PR levels in endometrial hyperplasia and carcinoma. Because of the dramatic decrease in PR content it is possible that prolonged progestin treatment leads to a decreased response to this kind of therapy. It is suggested that. in order to achieve a full benefit from long term progestin treatment. this therapy should be supplemented with estrogen. which is known to induce cytosolic ER and PR.
287. Plasma and urinary oestrogen levels in menopausal women receiving oestrogen therapy
KITCHIN. Y.. WHITEtfEAD.M. 1.. SHARPLES.M. J.. MINARDI.J. and CAMPBELL.S.. Department of Biochemical Endocrinology. Chelsea Hospital for Women. London SW3 6LT. England Unopposed natural oestrogen given cyclically for the relief of menopausal symptoms can result in the development of both cystic glandular hyperplasia and atypical hyperplasia. the incidence being dependent on oestrogen dose. Urinary total oestrogen excretion and plasma oestrone and oestradiol levels were determined both before and during therapy with high and low doses of three different natural oestrogen preparations in patients attending a menopause clinic. All three preparations. whether oestrone or oestradiol complexes. gave rise principally to oestrone in the plasma and resulted in a dose-dependent alteration of the oestrone’oestradiol ratio in favour of oestrone. In addition. high dose regimes were associated with urinary oestrogen and plasma oestrone levels more compatible with a hyperoestrogenic than pre-menopausal state. Reduction of dose is impracticable if therapy is to be effective. Therefore a regime. based on the present dosages. which does not cause endometrial hyperstimulation. such as the inclusion of a progestogen. is required.
208. Sex steroid receptors in normal and benign diseases of the Qm8n breast
SESHADRI. R.. SHAH.P. N. and SHINDE.S. R..* Division of Endocrinology. Cancer Research Institute and *Department of Surgery, Tata Memorial Hospital. Bombay. India Although the mammary gland is a target tissue for sex steroid. it is paradoxical that specific sex steroid receptors are absent in “normal” uninvolved breast tissues of radical mastectomized specimens. However, when I1 breast tissues from females below 25 years of age were analysed for these receptors. 7 were positive for estradiol (ER). 4 out of 8 for progesterone (PgR) and 6 out of 8 for dihydrotestosterone (DHTR). Under diseased states e.g. in fibrocystic disease. 2 out of 3 were positive for ER. while in ftbroadenoma. 7 out of 11 showed ER. 4 out of 10 PgR and 7 out of 10 DHTR. Based on these findings, we propose that although specific receptors for sex steroids are present in normal growing breasts. these somehow remained undetectable until they appear under altered hormonal environment or following neoplastic transformation.
856
between the different age groups particularly during the neonatal period and in early infancy. It is concluded that detailed knowledge of the age dependency of the normal plasma steroid pattern is a prerequisite for the understanding of pathological situations in pediatric endocrinology.
204. Role of dihydrotestusterone on 1,2,dimethylhydrazineinduced colon carcinogen&s
MEHTA.R. G.. FRISKS. C. M. and MOON, R. C., IIT Research Institute, Chicago. IL, 60616. U.S.A. Experiments were designed to study the effects of dihydrotestosterone (DHT) on the tumor incidence in 1.2.dimethylhydrazine dihydrochloride (DMH) treated BDIX male rats. Animals receiving IS mg/kg body weight of DMH. subcutaneously once a week for 20 weeks. developed adenocarcinemas in 60”,, of the cases I5 weeks following the last injection. The tumor incidence dropped to 27”,, in DMH treated gonadectemized rats. However. the incidence in DMH-treated castrated rats receiving DHT was comparable to that of intact rats. Quantitative measurement for DHT binding proteins was made on the cytosol of colons from DMH treated and control BDIX male rats. Scatchard analyses of the results showed that the colons from control animals did not have any unoccupied saturable binding sites whereas colon cytosol from DMH treated animals bound [‘HI-DHT with high affinity (Kd = 2.5 x IO-” M) and low capacity (II = 2Ofmolimg cytosol protein). DHT receptors were uniformly distributed throughout the colon. Increasing dosage of DMH beyond IS mg did not increase the number of binding sites. The results indicate that tumorigenesis of colon is hormone responsive and that the influence of sex steroid is mediated through specific carcinogen induced DHT receptors.
205. Plasma cortisol and testosterone levels in patients with idiopathic hirsutism during hypoglycemia
KO~IJAN~I~. A.. Department for Endocrinology and Metabolic Disorders. 61000 Ljubljana. Yugoslavia In 20 female patients with idiopathic hirsutism (IH). hypoglycemia was induced by means of i.v. insulin and the concentrations of plasma cortisol and testosterone were determined at 0. 30. 60. 90 and I20 min. Mean plasma cortisol levels in IH patients did not change with hypoglycemia. whilst a non-significant decrease of the mean plasma testosterone levels was observed during the test. In the control group consisting of 6 female patients with an intact hypothalamic-pituitary-adrenal axis. the mean concentration of plasma cortisol during hypoglycemia dropped at 30 min. whereafter an appropriate increase was observed. In these patients. mean concentrations of plasma testosterone increased at 30 and 60min and then dropped to the initial values. At 30 min a negative correlation between the mean plasma cortisol and testosterone levels was found in all subjects.
206 Regulation of steroid receptors in human endometrial hyperpbia
and carcinoma
VIHKO. R.. JANNE,0.. KAUPPILA.A.. KONTULA.K. and SYRJ~L~. P., Departments of Clinical Chemistry. Bio-
chemistry and Obstetrics and Gynecology. University of Oulu. SF-90220 Oulu 22. Finland Progestin treatment has been shown to be an effective form of therapy in about one-third of patients with advanced endometrial cancer. Regression of the tumor is probably due to a localized hormone effect on the tumor cells rather than a systemically mediated action. The purpose of this study was to investigate estrogen (ER) and progestin (PR)
receptors in hyperplastic and carcinomatous endometrium and to monitor the effects of progestin administration on their concentrations. Samples were obtained by curettage before and after 2-4 weeks of progestin treatment. Cytosolit unoccupied ER and cytosolic total PR were quantified by the method of Scatchard. The mean concentrations (fmol/mg cytosol protein) of ER were 137 and 161 and of PR 822 and 687 in the proliferative (n = 14) and secretory (n = 17) endometrium. respectively. In cystic glandular (n = 14) and adenomatous (n = 4) hyperplasia the concentrations were higher (ER 186 and 294: PR 1500 and 1423. respectively). whereas in endometrial carcinoma (it = 29) the PR level was lower (366) and ER was 190. Progestin administration led IO a decrease in ER and PR levels in endometrial hyperplasia and carcinoma. Because of the dramatic decrease in PR content it is possible that prolonged progestin treatment leads to a decreased response to this kind of therapy. It is suggested that. in order to achieve a full benefit from long term progestin treatment. this therapy should be supplemented with estrogen. which is known to induce cytosolic ER and PR.
287. Plasma and urinary oestrogen levels in menopausal women receiving oestrogen therapy
KITCHIN. Y.. WHITEtfEAD.M. 1.. SHARPLES.M. J.. MINARDI.J. and CAMPBELL.S.. Department of Biochemical Endocrinology. Chelsea Hospital for Women. London SW3 6LT. England Unopposed natural oestrogen given cyclically for the relief of menopausal symptoms can result in the development of both cystic glandular hyperplasia and atypical hyperplasia. the incidence being dependent on oestrogen dose. Urinary total oestrogen excretion and plasma oestrone and oestradiol levels were determined both before and during therapy with high and low doses of three different natural oestrogen preparations in patients attending a menopause clinic. All three preparations. whether oestrone or oestradiol complexes. gave rise principally to oestrone in the plasma and resulted in a dose-dependent alteration of the oestrone’oestradiol ratio in favour of oestrone. In addition. high dose regimes were associated with urinary oestrogen and plasma oestrone levels more compatible with a hyperoestrogenic than pre-menopausal state. Reduction of dose is impracticable if therapy is to be effective. Therefore a regime. based on the present dosages. which does not cause endometrial hyperstimulation. such as the inclusion of a progestogen. is required.
208. Sex steroid receptors in normal and benign diseases of the Qm8n breast
SESHADRI. R.. SHAH.P. N. and SHINDE.S. R..* Division of Endocrinology. Cancer Research Institute and *Department of Surgery, Tata Memorial Hospital. Bombay. India Although the mammary gland is a target tissue for sex steroid. it is paradoxical that specific sex steroid receptors are absent in “normal” uninvolved breast tissues of radical mastectomized specimens. However, when I1 breast tissues from females below 25 years of age were analysed for these receptors. 7 were positive for estradiol (ER). 4 out of 8 for progesterone (PgR) and 6 out of 8 for dihydrotestosterone (DHTR). Under diseased states e.g. in fibrocystic disease. 2 out of 3 were positive for ER. while in ftbroadenoma. 7 out of 11 showed ER. 4 out of 10 PgR and 7 out of 10 DHTR. Based on these findings, we propose that although specific receptors for sex steroids are present in normal growing breasts. these somehow remained undetectable until they appear under altered hormonal environment or following neoplastic transformation.