Insulin: Its role in the central control of reproduction

Physiology and Behavior

Volumn 133, Issue , 2014, Pages 197-206

  Sliwowska, Joanna H ^a   Fergani, Chrysanthi ^b   Gawałek, Monika ^a   Skowronska, Bogda ^c   Fichna, Piotr ^c   Lehman, Michael N ^b  

^a POZNA UNIVERSITY OF LIFE SCIENCES   (Poland)

^b UNIVERSITY OF MISSISSIPPI MEDICAL CENTER   (United States)

^c POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

Author keywords

AgRP; GnRH; Hypothalamus; Insulin receptors; Kisspeptin; POMC

Indexed keywords

GLUCOSE; GONADORELIN; INSULIN; KISSPEPTIN; LUTEINIZING HORMONE; KISS1 PROTEIN, HUMAN;

BLOOD BRAIN BARRIER; BRAIN; CENTRAL NERVOUS SYSTEM; ENERGY; ENERGY BALANCE; GLUCOSE HOMEOSTASIS; HOMEOSTASIS; HORMONE ACTION; HORMONE RELEASE; HUMAN; HYPOTHALAMUS; INSULIN DEPENDENT DIABETES MELLITUS; METABOLIC REGULATION; NERVE CELL; NONHUMAN; PRENATAL PERIOD; PRIORITY JOURNAL; REPRODUCTION; REVIEW; ANIMAL; CYTOLOGY; DRUG EFFECTS; ENERGY METABOLISM; METABOLISM; PHYSIOLOGY;

ANIMALS; BRAIN; ENERGY METABOLISM; GONADOTROPIN-RELEASING HORMONE; HUMANS; INSULIN; KISSPEPTINS; LUTEINIZING HORMONE; NEURONS; REPRODUCTION;

EID: 84902319712     PISSN: 00319384     EISSN: 1873507X     Source Type: Journal    
DOI: 10.1016/j.physbeh.2014.05.021     Document Type: Review

References (178)

1. Fernandez-Fernandez R., Martini A.C., Navarro V.M., Castellano J.M., Dieguez C., Aguilar E., et al. Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol 2006, 254-255:127-132.
2. Crown A., Clifton D.K., Steiner R.A. Neuropeptide signaling in the integration of metabolism and reproduction. Neuroendocrinology. 2007, 86:175-182.
3. Smith M.S., True C., Grove K.L. The neuroendocrine basis of lactation-induced suppression of GnRH: role of kisspeptin and leptin. Brain Res 2010, 1364:139-152.
4. Banting F.G., Best C.H., Collip J.B., Campbell W.R., Fletcher A.A. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 1922, 12:141-146.
5. Donato J. The central nervous system as a promising target to treat diabetes mellitus. Curr Top Med Chem 2012, 12:2070-2081.
6. Ghasemi R., Haeri A., Dargahi L., Mohamed Z., Ahmadiani A. Insulin in the brain: sources, localization and functions. Mol Neurobiol 2013, 47:145-171.
7. Silverman A.J., Antunes J.L., Abrams G.M., Nilaver G., Thau R., Robinson J.A., et al. The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections. J Comp Neurol 1982, 211:309-317.
8. Silverman A.J., Jhamandas J., Renaud L.P. Localization of luteinizing hormone-releasing hormone (LHRH) neurons that project to the median eminence. J Neurosci 1987, 7:2312-2319.
9. Jansen H.T., Hileman S.M., Lubbers L.S., Kuehl D.E., Jackson G.L., Lehman M.N. Identification and distribution of neuroendocrine gonadotropin-releasing hormone neurons in the ewe. Biol Reprod 1997, 56:655-662.
10. King J.C., Tobet S.A., Snavely F.L., Arimura A.A. LHRH immunopositive cells and their projections to the median eminence and organum vasculosum of the lamina terminalis. J Comp Neurol 1982, 209:287-300.
11. Lehman M.N., Newman S.W., Silverman A.J. Luteinizing hormone-releasing hormone in the vomeronasal system and terminal nerve of the hamster. Ann N Y Acad Sci 1987, 519:229-240.
12. Jennes L., Stumpf W.E. Gonadotropin-releasing hormone immunoreactive neurons with access to fenestrated capillaries in mouse brain. Neuroscience 1986, 18:403-416.
13. Clarke I.J., Cummins J.T. The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology 1982, 111:1737-1739.
14. Karsch F.J., Bowen J.M., Caraty A., Evans N.P., Moenter S.M. Gonadotropin-releasing hormone requirements for ovulation. Biol Reprod 1997, 56:303-309.
15. Dong Q., Lazarus R.M., Wong L.S., Vellios M., Handelsman D.J. Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. J Endocrinol 1991, 131:49-55.
16. Bucholtz D.C., Chiesa A., Pappano W.N., Nagatani S., Tsukamura H., Maeda K.I., et al. Regulation of pulsatile luteinizing hormone secretion by insulin in the diabetic male lamb. Biol Reprod 2000, 62:1248-1255.
17. Katayama S., Brownscheidle C.M., Wootten V., Lee J.B., Shimaoka K. Absent or delayed preovulatory luteinizing hormone surge in experimental diabetes mellitus. Diabetes 1984, 33:324-327.
18. Fergani C., Saifullizam A.K., Routly J.E., Smith R.F., Dobson H. Estrous behavior, luteinizing hormone and estradiol profiles of intact ewes treated with insulin or endotoxin. Physiol Behav 2012, 105:757-765.
19. Medina C.L., Nagatani S., Darling T.A., Bucholtz D.C., Tsukamura H., Maeda K., et al. Glucose availability modulates the timing of the luteinizing hormone surge in the ewe. J Neuroendocrinol 1998, 10:785-792.
20. Bergendahl M., Perheentupa A., Huhtaniemi I. Starvation-induced suppression of pituitary-testicular function in rats is reversed by pulsatile gonadotropin-releasing hormone substitution. Biol Reprod 1991, 44:413-419.
21. Williams N.I., Lancas M.J., Cameron J.L. Stimulation of luteinizing hormone secretion by food intake: evidence against a role for insulin. Endocrinology 1996, 137:2565-2571.
22. Hileman S.M., Schillo K.K., Hall J.B. Effects of acute, intracerebroventricular administration of insulin on serum concentrations of luteinizing hormone, insulin, and glucose in ovariectomized lambs during restricted and ad libitum feed intake. Biol Reprod 1993, 48:117-124.
23. Miller D.W., Blache D., Martin G.B. The role of intracerebral insulin in the effect of nutrition on gonadotrophin secretion in mature male sheep. J Endocrinol 1995, 147:321-329.
24. True C., Grove K.L., Smith M.S. Beyond leptin: emerging candidates for the integration of metabolic and reproductive function during negative energy balance. Front Endocrinol (Lausanne) 2011, 2:53.
25. Schneider J.E. Energy balance and reproduction. Physiol Behav 2004, 81:289-317.
26. Kosior-Korzecka U., Bobowiec R., Lipecka C. Fasting-induced changes in ovulation rate, plasma leptin, gonadotropins, GH, IGF-I and insulin concentrations during oestrus in ewes. J Veterinary Med Ser A 2006, 53:5-11.
27. Mackey D.R., Sreenan J.M., Roche J.F., Diskin M.G. Effect of acute nutritional restriction on incidence of anovulation and periovulatory estradiol and gonadotropin concentrations in beef heifers. Biol Reprod 1999, 61:1601-1607.
28. Wahab F., Zaman W.U., Shahab M. Differential response of the primate HPG axis to N-methyl-d, l-aspartate, but not to kisspeptin challenge under euglycemic and hypoglycemic conditions. Horm Metab Res 2012, 44:451-457.
29. Watanobe H., Yoneda M., Kohsaka A., Kakizaki Y., Suda T., Schioth H.B. Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats. Neuropeptides 2001, 35:45-49.
30. McClure T.J., Saunders J. Effects of withholding food for 0-72h on mating, pregnancy rate and pituitary function in female rats. J Reprod Fertil 1985, 74:57-64.
31. Kiyma Z., Alexander B.M., Van Kirk E.A., Murdoch W.J., Hallford D.M., Moss G.E. Effects of feed restriction on reproductive and metabolic hormones in ewes. J Anim Sci 2004, 82:2548-2557.
32. Alexander B.M., Kiyma Z., McFarland M., Van Kirk E.A., Hallford D.M., Hawkins D.E., et al. Influence of short-term fasting during the luteal phase of the estrous cycle on ovarian follicular development during the ensuing proestrus of ewes. Anim Reprod Sci 2007, 97:356-363.
33. Xu J., Kirigiti M.A., Grove K.L., Smith M.S. Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation: role of insulin and leptin. Endocrinology 2009, 150:4231-4240.
34. Dobson H., Smith R.F. What is stress, and how does it affect reproduction?. Anim Reprod Sci 2000, 60-61:743-752.
35. Bell R.H., Hye R.J. Animal models of diabetes mellitus: physiology and pathology. J Surg Res 1983, 35:433-460.
36. Kienast S.G., Fadden C., Steger R.W. Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat. Brain Res Bull 1993, 32:399-405.
37. Valdes C.T., Eliknd-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.
38. Bestetti G.E., Junker U., Locatelli V., Rossi G.L. Continuous subtherapeutic insulin counteracts hypothalamo-pituitary-gonadal alterations in diabetic rats. Diabetes 1987, 36:1315-1319.
39. Evans N.P., Dahl G.E., Padmanabhan V., Thrun L.A., Karsch F.J. Estradiol requirements for induction and maintenance of the gonadotropin-releasing hormone surge: implications for neuroendocrine processing of the estradiol signal. Endocrinology 1997, 138:5408-5414.
40. Medina C.L., Nagatani S., Darling T.A., Bucholtz D.C., Tsukamura H., Maeda K., et al. Glucose availability modulates the timing of the luteinizing hormone surge in the ewe. J Neuroendocrinol 1998, 10:785-792.
41. Fergani C., Saifullizam A.K., Routly J.E., Smith R.F., Dobson H. Estrous behavior, luteinizing hormone and estradiol profiles of intact ewes treated with insulin or endotoxin. Physiol Behav 2012, 105:757-765.
42. Fergani C., Routly J., Jones D., Pickavance L., Smith R., Dobson H. Kisspeptin, c-Fos and CRFR type 2 Co-expression in the hypothalamus after insulin-induced hypoglycaemia. Reprod Domest Anim 2014, 49:433-440.
43. Saifullizam A.K., Routly J.E., Smith R.F., Dobson H. Effect of insulin on the relationship of estrous behaviors to estradiol and LH surges in intact ewes. Physiol Behav 2010, 99:555-561.
44. Kawaguchi M., Funabashi T., Kimura F. Insulin-induced hypoglycemia does not impair the surge of luteinizing hormone secretion in the proestrous rat. Neurosci Lett 1998, 256:131-134.
45. Lujan M., MacTavish P., Krzemien A., Bradstock M., Vugt D. Estrogen-induced gonadotropin surge in rhesus monkeys is not inhibited by cortisol synthesis inhibition or hypoglycemia. Endocrine 2002, 19:169-176.
46. Clarke I.J., Horton R.J.E., Doughton B.W. Investigation of the mechanism by which insulin-induced hypoglycemia decreases luteinizing hormone secretion in ovariectomized ewes. Endocrinology 1990, 127:1470-1476.
47. Franks S., McCarthy M.I., Hardy K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 2006, 29:278-285.
48. Veiga-Lopez A., Ye W., Phillips D.J., Herkimer C., Knight P.G., Padmanabhan V. Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep. Biol Reprod 2008, 78:636-647.
49. Sharma Tejinder P., Herkimer C., West C., Ye W., Birch R., Robinson J.E., et al. Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep. Biol Reprod 2002, 66:924-933.
50. Abi Salloum B., Herkimer C., Lee J.S., Veiga-Lopez A., Padmanabhan V. Developmental programming: prenatal and postnatal contribution of androgens and insulin in the reprogramming of estradiol positive feedback disruptions in prenatal testosterone-treated sheep. Neuroendocrinology 2012, 153:2813-2822.
51. Lawson M.A., Jain S., Sun S., Patel K., Malcolm P.J., Chang R.J. Evidence for insulin suppression of baseline luteinizing hormone in women with polycystic ovarian syndrome and normal women. J Clin Endocrinol Metab 2008, 93:2089-2096.
52. Goodman R.L., Jansen H.T., Billings H.J., Coolen L.M., Lehman M.N. Neural systems mediating seasonal breeding in the ewe. J Neuroendocrinol 2010, 22:674-681.
53. Bakker J.M., van Bel F., Heijnen C.J. Neonatal glucocorticoids and the developing brain: short-term treatment with life-long consequences?. Trends Neurosci 2001, 24:649-653.
54. Matthews S.G. Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 2002, 13:373-380.
55. Meaney M.J., Szyf M., Seckl J.R. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends Mol Med 2007, 13:269-277.
56. Welberg L.A., Seckl J.R. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 2001, 13:113-128.
57. Phillips D.I., Barker D.J., Fall C.H., Seckl J.R., Whorwood C.B., Wood P.J., et al. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?. J Clin Endocrinol Metab 1998, 83:757-760.
58. Phillips D.I., Walker B.R., Reynolds R.M., Flanagan D.E., Wood P.J., Osmond C., et al. Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension 2000, 35:1301-1306.
59. Fowden A.L., Giussani D.A., Forhead A.J. Intrauterine programming of physiological systems: causes and consequences. Physiology 2006, 21:29-37.
60. Godfrey K.M., Barker D.J. Fetal nutrition and adult disease. Am J Clin Nutr 2000, 71:1344S-1352S.
61. Milner R.D., Hill D.J. Fetal growth control: the role of insulin and related peptides. Clin Endocrinol (Oxf) 1984, 21:415-433.
62. Ng S.F., Lin R.C., Laybutt D.R., Barres R., Owens J.A., Morris M.J. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 2010, 467:963-966.
63. Hales C.N., Barker D.J. The thrifty phenotype hypothesis. Br Med Bull 2001, 60:5-20.
64. Liu X., Qi Y., Gao H., Jiao Y., Gu H., Miao J., et al. Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats. J Clin Biochem Nutr 2013, 52:43-48.
65. Fernandez-Twinn D.S., Ozanne S.E. Mechanisms by which poor early growth programs type-2 diabetes, obesity and the metabolic syndrome. Physiol Behav 2006, 88:234-243.
66. Ravelli A.C., van Der Meulen J.H., Osmond C., Barker D.J., Bleker O.P. Obesity at the age of 50y in men and women exposed to famine prenatally. Am J Clin Nutr 1999, 70:811-816.
67. Roseboom T.J., van der Meulen J.H., Ravelli A.C., Osmond C., Barker D.J., Bleker O.P. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 2001, 185:93-98.
68. Ibanez L., Potau N., de Zegher F. Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab 2000, 85:2624-2626.
69. Ibanez L., Potau N., Ferrer A., Rodriguez-Hierro F., Marcos M.V., de Zegher F. Reduced ovulation rate in adolescent girls born small for gestational age. J Clin Endocrinol Metab 2002, 87:3391-3393.
70. Ibanez L., Lopez-Bermejo A., Diaz M., Marcos M.V. Endocrinology and gynecology of girls and women with low birth weight. Fetal Diagn Ther 2011, 30:243-249.
71. Bates G.W., Propst A.M. Polycystic ovarian syndrome management options. Obstet Gynecol Clin North Am 2012, 39:495-506.
72. Lim S.S., Norman R.J., Davies M.J., Moran L.J. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Rev 2013, 14:95-109.
73. Qin J.Z., Pang L.H., Li M.J., Fan X.J., Huang R.D., Chen H.Y. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 2013, 11:56.
74. Lakkakula B.V., Thangavelu M., Godla U.R. Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review. J Assist Reprod Genet 2013, 30:883-895.
75. Xita N., Tsatsoulis A. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies. J Clin Endocrinol Metab 2006, 91:1660-1666.
76. Sullivan E.L., Grove K.L. Metabolic imprinting in obesity. Forum Nutr 2010, 63:186-194.
77. Dyer J.S., Rosenfeld C.R. Metabolic imprinting by prenatal, perinatal, and postnatal overnutrition: a review. Semin Reprod Med 2011, 29:266-276.
78. Taylor P.D., McConnell J., Khan I.Y., Holemans K., Lawrence K.M., Asare-Anane H., et al. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol Regul Integr Comp Physiol 2005, 288:R134-R139.
79. Plagemann A., Harder T., Melchior K., Rake A., Rohde W., Dorner G. Elevation of hypothalamic neuropeptide Y-neurons in adult offspring of diabetic mother rats. Neuroreport 1999, 10:3211-3216.
80. McMillen I.C., Adam C.L., Muhlhausler B.S. Early origins of obesity: programming the appetite regulatory system. J Physiol 2005, 565:9-17.
81. Taylor P.D., Poston L. Developmental programming of obesity in mammals. Exp Physiol 2007, 92:287-298.
82. Clegg D.J., Benoit S.C., Reed J.A., Woods S.C., Dunn-Meynell A., Levin B.E. Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am J Physiol Regul Integr Comp Physiol 2005, 288:R981-R986.
83. Billington C.J., Briggs J.E., Grace M., Levine A.S. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991, 260:R321-R327.
84. Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997, 278:135-138.
85. Butler A.A., Marks D.L., Fan W., Kuhn C.M., Bartolome M., Cone R.D. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci 2001, 4:605-611.
86. Morton G.J., Cummings D.E., Baskin D.G., Barsh G.S., Schwartz M.W. Central nervous system control of food intake and body weight. Nature 2006, 443:289-295.
87. Levin B.E. Epigenetic influences on food intake and physical activity level: review of animal studies. Obesity (Silver Spring) 2008, 16(Suppl. 3):S51-S54.
88. Plagemann A., Harder T., Rake A., Melchior K., Rittel F., Rohde W., et al. Hypothalamic insulin and neuropeptide Y in the offspring of gestational diabetic mother rats. Neuroreport 1998, 9:4069-4073.
89. Kaati G., Bygren L.O., Edvinsson S. Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur J Hum Genet 2002, 10:682-688.
90. Kaati G., Bygren L.O., Pembrey M., Sjostrom M. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 2007, 15:784-790.
91. Aerts L., Van Assche F.A. Animal evidence for the transgenerational development of diabetes mellitus. Int J Biochem Cell Biol 2006, 38:894-903.
92. Benyshek D.C., Johnston C.S., Martin J.F. Glucose metabolism is altered in the adequately-nourished grand-offspring (F3 generation) of rats malnourished during gestation and perinatal life. Diabetologia 2006, 49:1117-1119.
93. Bygren L.O., Kaati G., Edvinsson S. Longevity determined by paternal ancestors' nutrition during their slow growth period. Acta Biotheor 2001, 49:53-59.
94. Jimenez-Chillaron J.C., Isganaitis E., Charalambous M., Gesta S., Pentinat-Pelegrin T., Faucette R.R., et al. Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice. Diabetes 2009, 58:460-468.
95. Pinheiro A.R., Salvucci I.D., Aguila M.B., Mandarim-de-Lacerda C.A. Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats. Clin Sci 2008, 114:381-392.
96. Thamotharan M., Garg M., Oak S., Rogers L.M., Pan G., Sangiorgi F., et al. Transgenerational inheritance of the insulin-resistant phenotype in embryo-transferred intrauterine growth-restricted adult female rat offspring. Am J Physiol Endocrinol Metab 2007, 292:E1270-E1279.
97. Pembrey M.E., Bygren L.O., Kaati G., Edvinsson S., Northstone K., Sjostrom M., et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 2006, 14:159-166.
98. Chowers I., Lavy S., Halpern L. Effect of insulin administered intracisternally on the glucose level of the blood and the cerebrospinal fluid in vagotomized dogs. Exp Neurol 1966, 14:383-389.
99. Woods S.C., Porte D. Effect of intracisternal insulin on plasma glucose and insulin in the dog. Diabetes 1975, 24:905-909.
100. Havrankova J., Schmechel D., Roth J., Brownstein M. Identification of insulin in rat brain. Proc Natl Acad Sci U S A 1978, 75:5737-5741.
101. Havrankova J., Roth J., Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 1978, 272:827-829.
102. Dorn A., Bernstein H.G., Rinne A., Ziegler M., Hahn H.J., Ansorge S. Insulin- and glucagonlike peptides in the brain. Anat Rec 1983, 207:69-77.
103. Dorn A., Rinne A., Bernstein H.G., Hahn H.J., Ziegler M. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay). J Hirnforsch 1983, 24:495-499.
104. Jezova D., Vigas M., Sadlon J. C-peptide-like material in rat brain: response to fasting and glucose ingestion. Endocrinol Exp 1985, 19:261-266.
105. Schechter R., Holtzclaw L., Sadiq F., Kahn A., Devaskar S. Insulin synthesis by isolated rabbit neurons. Endocrinology 1988, 123:505-513.
106. Young W.S. Periventricular hypothalamic cells in the rat brain contain insulin mRNA. Neuropeptides 1986, 8:93-97.
107. Margolis R.U., Altszuler N. Insulin in the cerebrospinal fluid. Nature 1967, 215:1375-1376.
108. Banks W.A., Jaspan J.B., Huang W., Kastin A.J. Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides 1997, 18:1423-1429.
109. Banks W.A. The source of cerebral insulin. Eur J Pharmacol 2004, 490:5-12.
110. Woods S.C., Porte D. Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 1977, 233:E331-E334.
111. Banks W.A., Kastin A.J. Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin. Peptides 1998, 19:883-889.
112. Stein L.J., Dorsa D.M., Baskin D.G., Figlewicz D.P., Porte D., Woods S.C. Reduced effect of experimental peripheral hyperinsulinemia to elevate cerebrospinal fluid insulin concentrations of obese Zucker rats. Endocrinology 1987, 121:1611-1615.
113. Baskin D.G., Stein L.J., Ikeda H., Woods S.C., Figlewicz D.P., Porte D., et al. Genetically obese Zucker rats have abnormally low brain insulin content. Life Sci 1985, 36:627-633.
114. Banks W.A., Jaspan J.B., Kastin A.J. Effect of diabetes mellitus on the permeability of the blood-brain barrier to insulin. Peptides 1997, 18:1577-1584.
115. Baura G.D., Foster D.M., Kaiyala K., Porte D., Kahn S.E., Schwartz M.W. Insulin transport from plasma into the central nervous system is inhibited by dexamethasone in dogs. Diabetes 1996, 45:86-90.
116. Brüning J.C., Gautam D., Burks D.J., Gillette J., Schubert M., Orban P.C., et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000, 289:2122-2125.
117. Kovacs P., Parlow A.F., Karkanias G.B. Effect of centrally administered insulin on gonadotropin-releasing hormone neuron activity and luteinizing hormone surge in the diabetic female rat. Neuroendocrinology 2002, 76:357-365.
118. Plum L., Schubert M., Bruning J.C. The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 2005, 16:59-65.
119. Cernea M., Phillips R., Padmanabhan V., Coolen L.M., Lehman M.N. Prenatal testosterone decreases co-expression of insulin receptors in KNDy neurons in adult ewes. Society for neuroscience annual meeting 2012.
120. Caraty A., Fabre-Nys C., Delaleu B., Locatelli A., Bruneau G., Karsch F.J., et al. Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe. Endocrinology 1998, 139:1752-1760.
121. Qi Y., Iqbal J., Oldfield B.J., Clarke I.J. Neural connectivity in the mediobasal hypothalamus of the sheep brain. Neuroendocrinology 2008, 87:91-112.
122. Gamba M., Pralong F.P. Control of GnRH neuronal activity by metabolic factors: the role of leptin and insulin. Mol Cell Endocrinol 2006, 254-255:133-139.
123. Kim H.H., DiVall S.A., Deneau R.M., Wolfe A. Insulin regulation of GnRH gene expression through MAP kinase signaling pathways. Mol Cell Endocrinol 2005, 242:42-49.
124. DiVall S.A., Williams T.R., Carver S.E., Koch L., Br, xFc, et al. Divergent roles of growth factors in the GnRH regulation of puberty in mice. J Clin Invest 2010, 120:2900-2909.
125. Jeong-Hyung Lee M.E.M., Hicks Deana J., Phillips Karen K., Trent Jeffery M., Weissman Bernard E., Welch Danny R. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 1996, 88:1731-1737.
126. de Roux N., Genin E., Carel J.C., Matsuda F., Chaussain J.L., Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003, 100:10972-10976.
127. Seminara S.B., Messager S., Chatzidaki E.E., Thresher R.R., Acierno J.S., Shagoury J.K., et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003, 349:1614-1627.
128. Seminara S.B. Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion. Front Neuroendocrinol 2005, 26:131-138.
129. Lehman M.N., Merkley C.M., Coolen L.M., Goodman R.L. Anatomy of the kisspeptin neural network in mammals. Brain Res 2010, 1364:90-102.
130. Lehman M.N., Coolen L.M., Goodman R.L. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology 2010, 151:3479-3489.
131. Cheng G., Coolen L.M., Padmanabhan V., Goodman R.L., Lehman M.N. The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 2010, 151:301-311.
132. Goodman R.L., Hileman S.M., Nestor C.C., Porter K.L., Connors J.M., Hardy S.L., et al. Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control activity of the GnRH pulse generator in ewes. Endocrinology 2013, 154:4259-4269.
133. Navarro V.M., Castellano J.M., McConkey S.M., Pineda R., Ruiz-Pino F., Pinilla L., et al. Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 2011, 300:E202-E210.
134. Frisch R.E. Body fat, menarche, fitness and fertility. Hum Reprod 1987, 2:521-533.
135. Plant T.M., Barker-Gibb M.L. Neurobiological mechanisms of puberty in higher primates. Hum Reprod Update 2004, 10:67-77.
136. Ahmed M.L., Ong K.K., Dunger D.B. Childhood obesity and the timing of puberty. Trends Endocrinol Metab 2009, 20:237-242.
137. Castellano J.M., Navarro V.M., Fernandez-Fernandez R., Nogueiras R., Tovar S., Roa J., et al. Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 2005, 146:3917-3925.
138. Roa J., Vigo E., Garcia-Galiano D., Castellano J.M., Navarro V.M., Pineda R., et al. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. Am J Physiol Endocrinol Metab 2008, 294:E1088-E1096.
139. Castellano J.M., Navarro V.M., Roa J., Pineda R., Sánchez-Garrido M.A., García-Galiano D., et al. Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences. Endocrinology 2009, 150:784-794.
140. Castellano J.M., Navarro V.M., Fernandez-Fernandez R., Roa J., Vigo E., Pineda R., et al. Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats. Diabetes 2006, 55:2602-2610.
141. Navarro V.M., Ruiz-Pino F., Sanchez-Garrido M.A., Garcia-Galiano D., Hobbs S.J., Manfredi-Lozano M., et al. Role of neurokinin B in the control of female puberty and its modulation by metabolic status. J Neurosci 2012, 32:2388-2397.
142. Luque R.M., Kineman R.D., Tena-Sempere M. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: analyses using mouse models and a cell line. Endocrinology 2007, 148:4601-4611.
143. Fergani C., Routly J.E., Jones D.N., Pickavance L.C., Smith R.F., Dobson H. Kisspeptin, c-Fos and CRFR type 2 expression in the preoptic area and mediobasal hypothalamus during the follicular phase of intact ewes, and alteration after LPS. Physiol Behav 2013, 110-111:158-168.
144. Qiu X., Dowling A.R., Marino J.S., Faulkner L.D., Bryant B., Bruning J.C., et al. Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells. Endocrinology 2013, 154:1337-1348.
145. Myers M.G., Olson D.P. Central nervous system control of metabolism. Nature 2012, 491:357-363.
146. Hill J.W., Elmquist J.K., Elias C.F. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab 2008, 294:E827-E832.
147. Sheppard K.M., Padmanabhan V., Coolen L.M., Lehman M.N. Prenatal programming by testosterone of hypothalamic metabolic control neurones in the ewe. J Neuroendocrinol 2011, 23:401-411.
148. Benoit S.C., Air E.L., Coolen L.M., Strauss R., Jackman A., Clegg D.J., et al. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci 2002, 22:9048-9052.
149. Konner A.C., Janoschek R., Plum L., Jordan S.D., Rother E., Ma X., et al. Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab 2007, 5:438-449.
150. Hill J.W., Elias C.F., Fukuda M., Williams K.W., Berglund E.D., Holland W.L., et al. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab 2010, 11:286-297.
151. Qiu J., Zhang C., Borgquist A., Nestor C.C., Smith A.W., Bosch M.A., et al. Insulin excites anorexigenic proopiomelanocortin neurons via activation of canonical transient receptor potential channels. Cell Metab 2014, 19:682-693.
152. Sato I., Arima H., Ozaki N., Watanabe M., Goto M., Hayashi M., et al. Insulin inhibits neuropeptide Y gene expression in the arcuate nucleus through GABAergic systems. J Neurosci 2005, 25:8657-8664.
153. Roa J., Herbison A.E. Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. Endocrinology 2012, 153:5587-5599.
154. Leranth C., MacLusky N.J., Shanabrough M., Naftolin F. Immunohistochemical evidence for synaptic connections between pro-opiomelanocortin-immunoreactive axons and LH-RH neurons in the preoptic area of the rat. Brain Res 1988, 449:167-176.
155. Norgren R.B., Lehman M.N. A double-label pre-embedding immunoperoxidase technique for electron microscopy using diaminobenzidine and tetramethylbenzidine as markers. J Histochem Cytochem 1989, 37:1283-1289.
156. Backholer K., Smith J.T., Rao A., Pereira A., Iqbal J., Ogawa S., Li Q., Clarke I.J. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology. 2010, 151:2233-2243.
157. Costa I.C., Carvalho H.N., Pacheco-Figueiredo L., Tomada I., Tomada N. Hormonal modulation in aging patients with erectile dysfunction and metabolic syndrome. Int J Endocrinol 2013, 2013:107869.
158. Boddi V., Barbaro V., McNieven P., Maggi M., Rotella C.M. Present and future association between obesity and hypogonadism in Italian male. Archivio italiano di urologia, andrologia: organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica/Associazione ricerche in urologia 2014, 86:26-32.
159. Law G.D.C., Maclehose R.F., Longnecker M.P. Obesity and time to pregnancy. Hum Reprod 2007, 22:414-420.
160. van der Steeg J.W., Steures P., Eijkemans M.J., Habbema J.D., Hompes P.G., Burggraaff J.M., et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod 2008, 23:324-328.
161. Maheshwari A., Stofberg L., Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology - a systematic review. Hum Reprod Update 2007, 13:433-444.
162. Rittenberg V., Seshadri S., Sunkara S.K., Sobaleva S., Oteng-Ntim E., El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 2011, 23:421-439.
163. Wang J.X., Davies M., Norman R.J. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ 2000, 321:1320-1321.
164. Chavarro J.E., Ehrlich S., Colaci D.S., Wright D.L., Toth T.L., Petrozza J.C., et al. Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction. Fertil Steril 2012, 98:109-116.
165. 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.
166. Rosenfield R.L., Barnes R.B., Cara J.F., Lucky A.W. Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. Fertil Steril 1990, 53:785-791.
167. Lungu A.O., Zadeh E.S., Goodling A., Cochran E., Gorden P. Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2012, 97:563-567.
168. Tosi F., Negri C., Perrone F., Dorizzi R., Castello R., Bonora E., et al. Hyperinsulinemia amplifies GnRH agonist stimulated ovarian steroid secretion in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2012, 97:1712-1719.
169. Pasquali R., Casimirri F., Vicennati V. Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Hum Reprod 1997, 12(Suppl. 1):82-87.
170. Tang T., Lord J.M., Norman R.J., Yasmin E., Balen A.H. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2012, 5:CD003053.
171. Pagan Y.L., Srouji S.S., Jimenez Y., Emerson A., Gill S., Hall J.E. Inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome: investigation of hypothalamic and pituitary contributions. J Clin Endocrinol Metab 2006, 91:1309-1316.
172. Witchel S.F., Tena-Sempere M. The Kiss1 system and polycystic ovary syndrome: lessons from physiology and putative pathophysiologic implications. Fertil Steril 2013, 100:12-22.
173. Nef S., Verma-Kurvari S., Merenmies J., Vassalli J.D., Efstratiadis A., Accili D., et al. Testis determination requires insulin receptor family function in mice. Nature 2003, 426:291-295.
174. Pitetti J.L., Calvel P., Zimmermann C., Conne B., Papaioannou M.D., Aubry F., et al. An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice. Mol Endocrinol 2013, 27:814-827.
175. Schoeller E.L., Albanna G., Frolova A.I., Moley K.H. Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility. Diabetes 2012, 61:1869-1878.
176. Gomez O., Ballester B., Romero A., Arnal E., Almansa I., Miranda M., et al. Expression and regulation of insulin and the glucose transporter GLUT8 in the testes of diabetic rats. Horm Metab Res 2009, 41:343-349.
177. Semple R.K., Savage D.B., Cochran E.K., Gorden P., O'Rahilly S. Genetic syndromes of severe insulin resistance. Endocr Rev 2011, 32:498-514.
178. Hammoud A.O., Meikle A.W., Reis L.O., Gibson M., Peterson C.M., Carrell D.T. Obesity and male infertility: a practical approach. Semin Reprod Med 2012, 30:486-495.