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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(3): 54-74

The developmental neuroendocrinology of reproduction and adaptation: lessons from animal research

A.G. Reznikov

  1. V.P. Komisarenko Institute of Endocrinology and Metabolism of National Academy of Medical Sciences of Ukraine, 04114 Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz67.03.054


Abstract

In order to commemorate the 30th anniversary of the establishing Department of Endocrinology of Reproduction and Adaptation at the V.P. Komisarenko Institute of Endocrinology and Metabolism (Kyiv, Ukraine), the results of animal research in the field of developmental neuroendocrinology of reproduction and adaptation in early ontogenesis are reviewed in the article. Special attitude is paid to sex differentiation of the brain and developmental programming of hypothalamic-pituitary-adrenal axis. Presented are reprogramming effects of perinatal steroids, stress, some drugs, and chemical endocrine disruptors on the developing brain. Phenomenology and neurochemical mechanisms underlying hormone-neurotransmitter imprinting of morphology of the hypothalamus, sexual behavior, reproductive and endocrine functions, and stress reactivity are under discussion. The results of the studies could contribute to prenatal prevention of neuroendocrine and behavioral disorders.

Keywords: brain; sexual differentiation; androgens; estrogens; glucocorticoids; neurotransmitters; prenatal stress; sexual behavior; stress reactivity; endocrine disruptors; rat.

Full text: (PDF, in English)

References

  1. Messer LC, Boone-Heinonen J, Mponwane L. et al. Developmental programming: priming disease susceptibility for subsequent generations. Current Epidemiol Rep. 2015;2(1):37-51. CrossRef PubMed PubMedCentral
  2. Vaiserman A. Early-life exposure to endocrine disrupting chemicals and later-life health outcomes: an epigenetic bridge? Aging Dis. 2014;6(6):419-29.
  3. Barouki R, Melén E, Herceg Z et al. Epigenetics as a mechanism linking developmental exposures to long-term toxicity. Environ Int. 2018;114:77-86. CrossRef PubMed PubMedCentral
  4. Dörner G. Hormones and brain differentiation. Amsterdam: Elsevier Sci, 1976;272 p.
  5. Dörner G. Hormone-dependent brain development and neuroendocrine prophylaxis. Exp Clin Endocrinol.1989;94:4-22. CrossRef PubMed
  6. Reznikov AG. Hormone-neurotransmitter imprinting in the neuroendocrine control of reproduction. New York: Harwood Acad Publ, 1994;90 r.
  7. Reznikov AG. Perinatal programming of disorders of endocrine functions and behavior. Kyiv: Naukova dumka, 2019;272 p. [Ukrainian].
  8. Reznikov AG. Neurotransmitters and brain sexual differentiation. In: Hormones and brain development. G. Dörner , M. Kawakami, eds. Amsterdam etc.: Elsevier/ North Holand, Biomed. Press. 1978;175-9.
  9. Reznikov AG. Sex hormones and the brain differentiation. Kiev: Naukova dumka, 1982;252 p. [Russian].
  10. Reznikov AG. Estrogen metabolites and biogenic amines as determinants of steroid-dependent brain differentiation In:Systemic hormones, neurotransmitters and brain development. G.Dörner et al., eds. Monogr. Neural Sci.V.12, Basel etc.: Karger, 1986; 96-102. CrossRef PubMed
  11. Reznikov AG, Nosenko ND. Catecholamines in steroiddependent brain development. J Steroid Biochem Molec Biol. 1995;53(1-6):349-53. CrossRef
  12. Nosenko ND, Reznikov AG. Sexual differentiation of the brain as a manifestation of its plasticity. Neurophysiology. 2001;33(2):125-34. CrossRef
  13. McCormick CM, Furey BF, Child M et al. Neonatal sex hormones have "organizational" effects on the hypothalamic-pituitary-adrenal axis of male rats. Brain Res. Dev Brain Res. 1998;105(2):295-307. CrossRef
  14. McEwen B, Coirini H, Westlund-Danielsson A et al. Steroid hormones as mediators of neural plasticity. J Steroid Biochem Mol Biol. 1991;39:223-32. CrossRef
  15. 15.Seale JV, Wood SA, Atkinson HC, Lightman SL et al. Organizational role for testosterone and estrogen on adult hypothalamic-pituitary-adrenal axis activity in the male rat. Endocrinology. 2005;146(4):1973-82. CrossRef PubMed
  16. Stanley H F, Borthwick NM, Fink G. Brain protein changes during development and sexual differentiation in the rat. Brain Res. 1986;370:215-22. CrossRef
  17. Whorf RC, Tobet SA. Expression of the Raf-1 protein in rat brain during development and its hormonal regulation in hypothalamus. J Neurobiol. 1992; 23:103-19. CrossRef PubMed
  18. Limareva AA. Effect of verapamil on the proteins distribution in the brain discrete structures in the neonatally androgenized female rats of early postnatal age. Pathology. 2008;5(2):29. [Ukrainian].
  19. MacLusky ND, Philip A, Hulburt C, Naftolin F. Estrogen formation in the developing rat brain: sex differences in aromatase activity during early postnatal life. Psychoneuroendocrinology. 1985;77(3):355-61. CrossRef
  20. Vreeburg JT, van der Vaart PD, van der Schoot P. Prevention of central defeminization but not masculinization in male rats by inhibition neonatally of oestrogen biosynthesis. J Endocrinol. 1977;74(3):375-82. CrossRef PubMed
  21. Reznikov AG, Nosenko ND. Prevention of the anovulatory syndrome and testosterone-induced rise in catecholamine level in the hypothalamus of newborn rats with steroid aromatase inhibitors. Exp Clin Endocrinol. 1987;90(5):185-9. CrossRef PubMed
  22. MacLusky NJ, Riskalla M, Krey L et al. Anovulation in female rats induced by neonatal administration of the catechol estrogens, 2-hydroxy-estradiol and 4-hydroxy-estradiol. Neuroendocrinology (Basel). 1983;37(5):321-7. CrossRef PubMed
  23. Hardin B, Gorski R. Sex differences and the effects of testosterone injections on biogenic amine levels in neonatal rat brain. Brain Res. 1973;62(1):286-90. CrossRef
  24. Reznikov AG, Nosenko ND, Demkiv LP. New evidences for participation of biogenic amines in androgen-dependent sexual differentiation of hypothalamic control of gonadotropin secretion in rats. Endokrinologie. 1979;73:11-9.
  25. Reznikov AG, Nosenko ND, Tarasenko L.V. Augmentation of sterilizing effect of neonatal androgenization with tropolone, catechol-O-metiltransferase inhibitor, in female rats. Neuroendocrinology (Basel). 1990;52:455-9. CrossRef PubMed
  26. Breuer H, Knuppen R, Ball P. Interactions between estrogens and catecholamines: biochemical and clinical aspects. In: Endocrinology of Sex. G. Dörner, ed. Leipzig: J.A. Barth, 1974; 185-94.
  27. Reznikov AG, Nosenko ND. Prevention of the anovulatory syndrome and testosterone-induced rise in catecholamine level in the hypothalamus of newborn rats with steroid aromatase inhibitors. Exp Clin Endocrinol. 1987; 90(5):185-9. CrossRef PubMed
  28. Nosenko ND, Reznikov AG. Increase of noradrenaline contents in the hypothalamus of neonatal female rats under the influence of 4-hydroxyestradiol-17beta. Biull Éksp Biol Med. 1990;109(6):555-6. [Russian]. CrossRef
  29. Reznikov AG, Nosenko ND. It is possible that noradrenaline is the biogenic monoamine responsible for androgen-dependent sexual brain differentiation. Exp Clin Endocrinol. 1983;81(1):91-3. CrossRef PubMed
  30. Elsinga PH, Hendrikse NH, Vaalburg W, van Waarde A. PET studies on P-glycoprotein function in blood-brain barrier: how it affects uptake and binding of drugs within the CNS. Current Pharm Des. 2004;10(13):1493-503. CrossRef PubMed
  31. Matthews SG. Antenatal glucocorticoids and the developing brain: mechanisms of action. Semin Neonatal. 2001;6:309-17. CrossRef PubMed
  32. Seckl J.R. Prenatal glucocorticoids and long-term programming. Eur J Endocr. 2004;151:U49-U62. CrossRef PubMed
  33. Chang YP. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. Korean J Pediatr. 2014;57(3):101-9. CrossRef PubMed PubMedCentral
  34. Reznikov AG, Nosenko ND, Tarasenko LV. Prenatal stress and glucocorticoid effects on the developing genderrelated brain. J Steroid Biochem Mol Biol. 1999;69(1- 6):109-15. CrossRef
  35. Reznikov A, Nosenko N, Tarasenko L et al. Neuroendocrine disorders in adult rats treated prenatally with hydrocortisone acetate. Exp Toxicol Pathol. 2008; 60 (6):489-97. CrossRef PubMed
  36. Sinitsin PV, Tarasenko LV, Reznikov AG. Modifications of reactions of the hypothalamo-hypophyseal-adrenocortical system to noradrenergic and corticotropic stimulations in rats subjected to prenatal hydrocortisone treatment. Neurophysiology. 2005;37(1):21-5. CrossRef
  37. Dygalo NN, Naumenko EV. Hydrocortisone modification during intrauterine development of the activity of brain tyrosine hydroxylase in adult white rats. Ontogenez. 1988;19(3):319-22. [Russian].
  38. Brodie B, Costa E, Dlabac A et al. Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamine. J Pharmacol Exp Ther. 1966;154:493-8.
  39. Pereira OC, Arena AC, Yasuhara F, Kempinas WG. Effects of prenatal hydrocortisone acetate exposure on fertility and sexual behavior in male rats. Regul Toxicol Pharmacol. 2003;38:36-42. CrossRef
  40. Holson RR, Gough B, Sullivan P. Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. Neurotoxic Terat. 1995;17:393-401. CrossRef
  41. Oliveira M, Leão P, Rodrigues AJ et al. Programming effects of antenatal corticosteroids exposure in male sexual behavior. J Sex Med. 2011;8(7):1965-74. CrossRef PubMed
  42. Tarasenko LV. Metabolism of testosterone in the brain of rats exposed to dexamethasone in the prenatal period. Endokrynologia. 2001;6:293. [Ukrainian].
  43. Nosenko ND. Formation of the sex dimorphism and biogenic monoamines turnover in rats affected with hydrocortisone during prenatal ontogenesis. Endokrynologia. 1999; 4:106-110. [Ukrainian].
  44. Reznikov AG, Limareva AA. Modulation of puberty terms and sexual behavior of rats after prenatal exposure to methyldopa, phenibut and stress. Int J Physiol Pathophysiol. 2018; 9(1):27-35. CrossRef
  45. Nosenko ND. Effect of prenatal use of methyldopa and phenibut on the formation of stress reactivity of HPA axis in adult rats under normal conditions and in disturbed state as a result of prenatal stress. Endokrynologia. 2015;20(4):710-5. [Ukrainian].
  46. Nosenko ND, Sinitsyn PV, Reznikov AG. Role of calcium signaling in the development of prenatal stress-induced functional modifications of the hypothalamo-pituitaryadrenal axis. Neurophysiology. 2010;42(4):251-7. CrossRef
  47. Tarasenko LV. Features of sexual behavior formation in prenatal stressed rats under the conditions of action of nimodipine during the critical period of sexual differentiation of the brain. Endokrynologia. 2014;19(3):204-9. [Ukrainian].
  48. Biessels GJ, Laak MP, Kamal A, Gispen WH. Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocindiabetic rats. Brain Res. 2005;1035 (1):86-93. CrossRef PubMed
  49. Ward IL. Prenatal stress feminizes and demasculinizes the behavior of males. Science. 1972;175:82-4. CrossRef PubMed
  50. Dörner G, Geier T, Ahrens L. Prenatal stress as possible aetiogenic factor of homosexuality in human males. Endokrinologie. 1980;75:365-8.
  51. Dörner G, Schenk B, Schmiedel B, Ahrens L. Stressful events in prenatal life of bi- and homosexual men. Exper Clin Endocrinol. 1983;81:83-7. CrossRef PubMed
  52. Reznikov AG, Sinitsyn PV, Tarasenko LV. Responses of the hypothalamic-pituitary-adrenal axis to noradrenergic and hormonal stimulation in prenatally stressed rats. Neurophysiology. 1999;31(2):112-4. CrossRef
  53. Reznikov AG, Nosenko ND. Early postnatal changes in sexual dimorphism of catecholamine and indolamine contents in the brain of prenatally stressed rats. Neuroscience. 1996;70(2):547-51. CrossRef
  54. Reznikov AG, Nosenko ND, Tarasenko LV et al. Early and long-tern neuroendocrine effects of prenatal stress in male and female rats. Neurosci Behav Physiol. 2001;31(1):1-5. CrossRef PubMed
  55. Reznikov AG, Nosenko ND, Tarasenko LV. Opioids are responsible for neurochemical feminization of the brain in prenatally stressed male rats. Neuroendocrinol Lett. 2005;26(1):35-8.
  56. Nosenko ND, Reznikov AG. Prenatal stress and sexual differentiation of monoaminergic brain systems. Neurophysiology. 2001;33(3):197-206. CrossRef
  57. Reznikov A, Nosenko N, Tarasenko L et al. Prenatal dexamethasone prevents early and long-lasting neuroendocrine and behavioral effects of maternal stress on male offspring. Fiziol Zh. 2008;54(5):28-38. [Ukrainian].
  58. Reznikov AG, Pyshak VP, Nosenko ND et al. Prenatal stress and neuroendocrine pathology. Chernovtsy: Medakademia Publ. 2004;320 p. [Russian].
  59. Reznikov AG, Tarasenko LV. Hormonal protection of gender-related peculiarities of testosterone metabolism in the brain of prenatally stressed rats. Neuroendocrinol Lett. 2007;28(5):671-4.
  60. Nosenko ND, Limareva AA, Reznikov A. Preventive effect of nimodipine on early postnatal modifications of the protein spectrum in the brain of rats subjected to prenatal stress. Neurophysiology. 2012;44(1):20-5. CrossRef
  61. Tarasenko LV. Effect of prenatal administration of bendorphin on androgen metabolism in the brain of newborn rats. Zaporozhskiy Med Zh. 2005; No 3:113. [Ukrainian].
  62. Dörner G, Gotz F, Docke WD. Prevention of demasculinization and feminization of the brain in prenatally stressed male rats by perinatal androgen treatment. Exp Clin Endocrinol. 1983;81:88-90. CrossRef PubMed
  63. Rohde W, Ohkawa T, Gotz F et al. Sex-specific effects on the fetal neuroendocrine system during an acute stress in late pregnancy of rat and the influence of a simultaneous treatment by tyrosine. Exp Clin Endocrinol. 1989;94(1):23-42. CrossRef PubMed
  64. Rohde W, Okava T, Shtal F et al. Changes in the neuroendocrine system of rat fetuses during an acute stress in late pregnancy. In: Ontogenetic and genetic evolutionary aspects of neuroendocrine regulation of stress. Novosibirsk: Nauka, 1990;28-40. [Russian].
  65. Kashon ML, Ward OB, Grisham W, Ward IL. Prenatal b-endorphin can modulate some aspects of sexual differentiation in rats. Behav Neurosci. 1992;106: 555-62. CrossRef PubMed
  66. Ward OB, Monaghan EP, Ward IL. Naltrexone blocks the effects of prenatal stress on sexual behavior differentiation in male rats. Pharmac Biochem Behav. 1986;25:573-6. CrossRef
  67. Dömer G, Gotz F, Rohde W et al. Genetic and epigenetic effects on sexual brain organization mediated by sex hormones. Neuroendocrinol Lett. 2001;22:403-9.
  68. Darbre PD. Overview of air pollution and endocrine disorders. Int J Gen Med. 2018;11:191-207. CrossRef PubMed PubMedCentral
  69. Kabir ER, Rahman MS, Rahman I. A review on endocrine disruptors and their possible impacts on human health. Environ Toxicol Pharmacol. 2015; 40(1):241-58. CrossRef PubMed
  70. Sidorkiewicz I, Zaręba K, Wołczyński S, Czerniecki J. Endocrine-disrupting chemicals - Mechanisms of action on male reproductive system. Toxicol Ind Health. 2017;33(7):601-9. CrossRef PubMed
  71. Pinto A, Carvalho D. Human infertility: are endocrine disruptors to blame? Endocr Connect. 2013;2(3):R15-R29. CrossRef PubMed PubMedCentral
  72. Louis GMB. Persistent environmental pollutants and couple fecundity: an overview. Reproduction. 2014;147:R97-R104. CrossRef PubMed PubMedCentral
  73. Bonde JP, Meulengracht FE, Rimborg S, et al. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and metaanalysis. Hum Reprod Update. 2017;23:104-25. CrossRef PubMed PubMedCentral
  74. Foster PM, Cattley RC, Mylchreest E. Effects of di-n-butyl phthalate (DBP) on male reproductive development in the rat: implications for human risk assessment. Food Chem Toxicol. 2000;38:S97-S99. CrossRef
  75. Reznikov AG, Sachynska OV, Limareva AA, et al. Hypersexual behavior and hyperandrogenism in F1 male rats caused by dibutyl phtalate treatment of pregnant females. Int J Physiol Pathophysiol., 2018;9(3): 203-212. CrossRef
  76. Wang Y, Song L, Hong X, et al. Low concentrations monobutyl phthalate stimulates steroidogenesis by facilitating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1). Chem Biol Interact. 2006,164(1-2):15-24. CrossRef PubMed
  77. Chen X, Zhou QH, Leng L et al. Effects of di(n-butyl) and monobutyl phthalate on steroidogenesis pathways in the murine Leydig tumor cell line MLTC-1. Environ Toxicol Pharmacol. 2013;36(2):332-338. CrossRef PubMed
  78. Clewell RA, Kremer JJ, Williams CC, et al. Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats. Toxicology. 2009;8:80-90. CrossRef PubMed
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