problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201056523-29problendo-4749Research ArticleСтатьиArticlesФункциональное состояние гипоталамо-гипофизарно-гонадной системы при сахарном диабетеFunctional state of the hypothalamic-pituitary-gonadal axis in diabetes mellitusShpakovA Oalex_shpakov@list.ru201015102010565ТОМ 56, №5 (2010)2329Copyright © Shpakov A.O., 20102010Shpakov A.O.Shpakov A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/4749

У больных сахарным диабетом (СД) наблюдается широкий спектр нарушений репродуктивной системы. Предполагается, что в их основе лежат изменения функциональной активности гипоталамо-гипофизарно-гонадной системы (ГГГС) и чувствительности тканей репродуктивной системы к регуляторному действию гормонов. В обзоре проанализированы данные литературы и результаты собственных исследований, касающиеся синтеза и секреции гипоталамического рилизинг-фактора лютеинизирующего гормона, гипофизарных гонадотропных гормонов и стероидных гормонов, а также чувствительности к ним тканей-мишеней при СД 1-го и 2-го типов. Показано, что уровни инсулина и глюкозы являются ключевыми факторами, влияющими на функционирование всех звеньев ГГГС при СД. Сделан вывод о том, что улучшение контроля уровня глюкозы является одним из важнейших подходов к коррекции и восстановлению репродуктивных функций у больных СД.

Diabetic patients present with a wide variety of reproductive disorders supposed to be underlain by changes in the functional activity of the hypothalamic-pituitary-gonadal axis (HPGA) and sensitivity of the reproductive system tissues to the regulatory hormonal action. The objective of the present review is to analyse the literature data and the results of original studies pertinent to the biosynthesis and secretion of hypothalamic LH releasing factor, pituitary gonadotropic hormones, steroid hormones, and susceptibility of their target tissues in patients with types 1 and 2 diabetes mellitus. It is concluded that the improvement of control over blood glucose levels constitutes a most efficacious approach to the correction and normalization of reproductive function in diabetic patients.

гипоталамо-гипофизарно-гонадная системалютеинизирующий гормонрепродуктивная системасахарный диабетстероидные гормоныhypothalamic-pituitary-gonadal axisluteinizing hormonereproductive systemdiabetes mellitussteroid hormonesReferencesValdes C.T., Elkind-Hirsch K.E., Rogers D.G., Adelman J.P. The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement. Endocrinology 1991;128:433-440.Valdes C.T., Elkind-Hirsch K.E., Rogers D.G., Adelman J.P. The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement. Endocrinology 1991;128:433-440.Tanaka T., Nagatani S., Bucholtz D.C.et al. Central action of insulin regulates pulsatile luteinizing hormone secretion in the diabetic sheep model. Biol Reprod 2000;62:1256-1261.Tanaka T., Nagatani S., Bucholtz D.C.et al. Central action of insulin regulates pulsatile luteinizing hormone secretion in the diabetic sheep model. Biol Reprod 2000;62:1256-1261.Burcelin R., Thorens B., Glauser M. et al. Gonadotropin-releasing hormone secretion from hypothalamic neurons stimulation by insulin and potentiation by leptin. Endocrinology 2003;144:4484-4491.Burcelin R., Thorens B., Glauser M. et al. Gonadotropin-releasing hormone secretion from hypothalamic neurons stimulation by insulin and potentiation by leptin. Endocrinology 2003;144:4484-4491.Clough R.W., Kienast S.G., Steger R.W. Reproductive endocrinopathy in acute streptozotocin-induced diabetic male rats. Endocrine 1998;8:37-43.Clough R.W., Kienast S.G., Steger R.W. Reproductive endocrinopathy in acute streptozotocin-induced diabetic male rats. Endocrine 1998;8:37-43.Dong Q., Lazarus R.M., Wong L.S. et al. Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. J Endocrinol 1991;131:49-55.Dong Q., Lazarus R.M., Wong L.S. et al. Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. J Endocrinol 1991;131:49-55.Baccetti B., la Marca A., Piomboni P. et al. Insulin-dependent diabetes in men is associated with hypothalamic-pituitary derangement and with impairment in semen quality. Hum Reprod 2002;17:2673-2677.Baccetti B., la Marca A., Piomboni P. et al. Insulin-dependent diabetes in men is associated with hypothalamic-pituitary derangement and with impairment in semen quality. Hum Reprod 2002;17:2673-2677.La Marca A., Morgante G., De Leo V. Evaluation of hypothalamic-pituitary-adrenal axis in amenorrhoeic women with insulin-dependent diabetes. Hum Reprod 1999;14:298-302.La Marca A., Morgante G., De Leo V. Evaluation of hypothalamic-pituitary-adrenal axis in amenorrhoeic women with insulin-dependent diabetes. Hum Reprod 1999;14:298-302.Adashi E.Y., Hsueh A.J., Yen S.S. Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981;108: 1441-1449.Adashi E.Y., Hsueh A.J., Yen S.S. Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981;108: 1441-1449.Oltmanns K.M., Fruehwald-Schultes B., Kern W. et al. Hypoglycemia, but not insulin, acutely decreases LH and T secretion in men. J Clin Endocrinol Metab 2001;86:4913-4919.Oltmanns K.M., Fruehwald-Schultes B., Kern W. et al. Hypoglycemia, but not insulin, acutely decreases LH and T secretion in men. J Clin Endocrinol Metab 2001;86:4913-4919.Cates P.N., O'Byrne K.T. The area postrema mediates insulin hypoglycemia-induced suppression of pulsatile LH secretion in the female rat. Brain Res 2000;853:151-155.Cates P.N., O'Byrne K.T. The area postrema mediates insulin hypoglycemia-induced suppression of pulsatile LH secretion in the female rat. Brain Res 2000;853:151-155.Chen M.D., Ordog T., O'Byrne K.T. et al. The insulin hypoglycemia-induced inhibition of gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: roles of vasopressin and corticotropin-releasing factor. Endocrinology 1996;137:2012-2021.Chen M.D., Ordog T., O'Byrne K.T. et al. The insulin hypoglycemia-induced inhibition of gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: roles of vasopressin and corticotropin-releasing factor. Endocrinology 1996;137:2012-2021.Levin B.E., Dunn-Meynell A.A., Routh V.H. Brain glucose sensing and body energy homeostasis: role in obesity and diabetes. Am J Physiol 1999;276:1223-1231.Levin B.E., Dunn-Meynell A.A., Routh V.H. Brain glucose sensing and body energy homeostasis: role in obesity and diabetes. Am J Physiol 1999;276:1223-1231.Pitteloud N., Hardin M., Dwyer A.A. et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005;90:2636-2641.Pitteloud N., Hardin M., Dwyer A.A. et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005;90:2636-2641.Sudha S., Valli G., Julie M.P. et al. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats. Exp Clin Endocrinol Diabet 2000;108:14-20.Sudha S., Valli G., Julie M.P. et al. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats. Exp Clin Endocrinol Diabet 2000;108:14-20.Tanaka M., Nakaya S., Kumai T. et al. Impaired testicular function in rats with diet-induced hypercholesterolemia and/or streptozotocin-induced diabetes mellitus. Endocrinol Res 2001;27:109-117.Tanaka M., Nakaya S., Kumai T. et al. Impaired testicular function in rats with diet-induced hypercholesterolemia and/or streptozotocin-induced diabetes mellitus. Endocrinol Res 2001;27:109-117.Ballester J., Munoz M.C., Dominguez J. et al. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004;25:706-719.Ballester J., Munoz M.C., Dominguez J. et al. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004;25:706-719.Ballester J., Munoz M.C., Dominguez J. et al. Tungstate administration impoves the sexual and reproductive function in female rats with streptozotocin-induced diabetes. Hum Reprod 2007;22:2128-2135.Ballester J., Munoz M.C., Dominguez J. et al. Tungstate administration impoves the sexual and reproductive function in female rats with streptozotocin-induced diabetes. Hum Reprod 2007;22:2128-2135.Katayama S., Brownscheidle C.M., Wootten V. et al. Absent or delayed preovulatory luteinizing hormone surge in experimental diabetes mellitus. Diabetes 1984;33:324-327.Katayama S., Brownscheidle C.M., Wootten V. et al. Absent or delayed preovulatory luteinizing hormone surge in experimental diabetes mellitus. Diabetes 1984;33:324-327.Bruning J.C., Gautam D., Burks D.J. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289:2122-2125.Bruning J.C., Gautam D., Burks D.J. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289:2122-2125.Munoz M.C., Barbera A., Dominguez J. et al. Effects of tungstate, a new potential oral antidiabetic agent, on Zucker diabetic fatty rats. Diabetes 2001;50:131-138.Munoz M.C., Barbera A., Dominguez J. et al. Effects of tungstate, a new potential oral antidiabetic agent, on Zucker diabetic fatty rats. Diabetes 2001;50:131-138.Bhatia V., Chaudhuri A., Tomar R. et al. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabet Care 2006;29:2289-2294.Bhatia V., Chaudhuri A., Tomar R. et al. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabet Care 2006;29:2289-2294.Chandel A., Dhindsa S., Topiwala S. et al. Testosterone concentration in young patients with diabetes. Diabet Care 2008;31:2013-2017.Chandel A., Dhindsa S., Topiwala S. et al. Testosterone concentration in young patients with diabetes. Diabet Care 2008;31:2013-2017.Van Dam E.W.C.M., Dekker J.M., Lentjes E.G.W.M. et al. Steroids in adult men with type 1 diabetes. Diabet Care 2003;26:1812-1818.Van Dam E.W.C.M., Dekker J.M., Lentjes E.G.W.M. et al. Steroids in adult men with type 1 diabetes. Diabet Care 2003;26:1812-1818.Alexopoulou O., Jamart J., Maiter D. et al. Erectile dysfunction and lower androgenicity in type 1 diabetic patients. Diabet Metab 2001;27:329-336.Alexopoulou O., Jamart J., Maiter D. et al. Erectile dysfunction and lower androgenicity in type 1 diabetic patients. Diabet Metab 2001;27:329-336.Dandona P., Dhindsa S., Chaudhuri A. et al. Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. Curr Mol Med 2008;8:816-828.Dandona P., Dhindsa S., Chaudhuri A. et al. Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. Curr Mol Med 2008;8:816-828.Kapoor D., Aldred H., Clark S. et al. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes. Diabet Care 2007;30:911-917.Kapoor D., Aldred H., Clark S. et al. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes. Diabet Care 2007;30:911-917.Quinn M.A., Ruffe H., Brown J.B., Ennis G. Circulating gonadotropins and urinary oestrogens in postmenopausal diabetic women. Aust N Z J Obstet Gynaecol 1981;21:234-236.Quinn M.A., Ruffe H., Brown J.B., Ennis G. Circulating gonadotropins and urinary oestrogens in postmenopausal diabetic women. Aust N Z J Obstet Gynaecol 1981;21:234-236.Kelestimur F., Unluhizarci K., Baybuga H. et al. Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus. Fertil Steril 2006;86:405-410.Kelestimur F., Unluhizarci K., Baybuga H. et al. Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus. Fertil Steril 2006;86:405-410.Kajaia N., Binder H., Dittrich R. et al. Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome. Eur J Endocrinol 2007;157:499-507.Kajaia N., Binder H., Dittrich R. et al. Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome. Eur J Endocrinol 2007;157:499-507.Codner E., Mook-Kanamori D., Bazaes R.A. et al. Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide. J Clin Endocrinol Metab 2005;90:3939-3945.Codner E., Mook-Kanamori D., Bazaes R.A. et al. Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide. J Clin Endocrinol Metab 2005;90:3939-3945.Feldman H.A., Longcope C., Derby C.A. et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87:589-598.Feldman H.A., Longcope C., Derby C.A. et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87:589-598.Betancourt-Albrecht M., Cunningham G.R. Hypogonadism and diabetes. Int J Impot Res 2003;15:Suppl 4:S14-S20.Betancourt-Albrecht M., Cunningham G.R. Hypogonadism and diabetes. Int J Impot Res 2003;15:Suppl 4:S14-S20.Шпаков А.О., Деркач К.В., Бондарева В.М. Изменение гормональной чувствительности аденилатциклазной сигнальной системы тестикулярной ткани крыс в условиях неонатального стрептозотоцинового диабета. Бюл экспер. биол 2009;148:9:282-286.Шпаков А.О., Деркач К.В., Бондарева В.М. Изменение гормональной чувствительности аденилатциклазной сигнальной системы тестикулярной ткани крыс в условиях неонатального стрептозотоцинового диабета. Бюл экспер. биол 2009;148:9:282-286.Шпаков А.О., Бондарева В.М., Чистякова О.В. Функциональное состояние аденилатциклазной сигнальной системы в репродуктивных тканях крыс с экспериментальным диабетом 1-го типа. Цитология 2010;52:2:177-183.Шпаков А.О., Бондарева В.М., Чистякова О.В. Функциональное состояние аденилатциклазной сигнальной системы в репродуктивных тканях крыс с экспериментальным диабетом 1-го типа. Цитология 2010;52:2:177-183.Steger R.W., Kienast S.G. Effect of continuous versus delayed insulin replacement on sex behavior and neuroendocrine function in diabetic male rats. Diabetes 1990;39:942-948.Steger R.W., Kienast S.G. Effect of continuous versus delayed insulin replacement on sex behavior and neuroendocrine function in diabetic male rats. Diabetes 1990;39:942-948.Arreola F., Paniagua R., Herrera J. et al. Low plasma zinc and androgen in insulin-dependent diabetes mellitus. Arch Androl 1986;16:151-154.Arreola F., Paniagua R., Herrera J. et al. Low plasma zinc and androgen in insulin-dependent diabetes mellitus. Arch Androl 1986;16:151-154.Grossmann M., Thomas M.C., Panagiotopoulos S. et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 2008;93:1834-1840.Grossmann M., Thomas M.C., Panagiotopoulos S. et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 2008;93:1834-1840.Ebeling P., Stenman U.H., Seppala M., Koivisto V.A. Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy man. J Endocrinol 1995;146:63-69.Ebeling P., Stenman U.H., Seppala M., Koivisto V.A. Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy man. J Endocrinol 1995;146:63-69.Ding E.L., Song Y., Malik V.S., Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes. JAMA 2006;295:1288-1299.Ding E.L., Song Y., Malik V.S., Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes. JAMA 2006;295:1288-1299.Kalme T., Seppala M., Qiao Q. et al. Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men. J Clin Endocrinol Metab 2005;90:1550-1556.Kalme T., Seppala M., Qiao Q. et al. Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men. J Clin Endocrinol Metab 2005;90:1550-1556.Pitteloud N., Mootha V.K., Dwyer A.A. et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabet Care 2005;28:1636-1642.Pitteloud N., Mootha V.K., Dwyer A.A. et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabet Care 2005;28:1636-1642.Phillips G.B., Tuck C.H., Jing T.Y. et al. Association of hyperandrogenemia and hyperestrogenemia with type 2 diabetes in Hispanic postmenopausal women. Diabet Care 2000;23:74-79.Phillips G.B., Tuck C.H., Jing T.Y. et al. Association of hyperandrogenemia and hyperestrogenemia with type 2 diabetes in Hispanic postmenopausal women. Diabet Care 2000;23:74-79.Plymate S.R., Matej L.A., Jones R.E., Friedl K.E. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 1988;67:460-464.Plymate S.R., Matej L.A., Jones R.E., Friedl K.E. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 1988;67:460-464.Pasquali R., Casimirri F., de Iasio R. et al. Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. J Clin Endocrinol Metab 1995;80:654-658.Pasquali R., Casimirri F., de Iasio R. et al. Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. J Clin Endocrinol Metab 1995;80:654-658.Codner E., Escobar-Morreale H.F. Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2007;92:1209-1216.Codner E., Escobar-Morreale H.F. Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2007;92:1209-1216.Goodman-Gruen D., Barrett-Connor E. Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes 2000;23:912-918.Goodman-Gruen D., Barrett-Connor E. Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes 2000;23:912-918.Corona G., Mannucci E., Petrone L. et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res 2006;18:190-197.Corona G., Mannucci E., Petrone L. et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res 2006;18:190-197.Pasquali R., Macor C., Vicennati V. et al. Effect of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men. Metabolism 1997;46:526-529.Pasquali R., Macor C., Vicennati V. et al. Effect of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men. Metabolism 1997;46:526-529.Alrefai H., Allababidi H., Levy S., Levy J. The endocrine system in diabetes mellitus. Endocrine 2002;18:105-119.Alrefai H., Allababidi H., Levy S., Levy J. The endocrine system in diabetes mellitus. Endocrine 2002;18:105-119.

The authors declare that there are no conflicts of interest present.