Mini-Review| Volume 24, ISSUE 6, P330-337, December 2011

Endocrine Modulation of the Adolescent Brain: A Review

  • Pilar Vigil
    Address correspondence to: Pilar Vigil, MD, PhD, Unidad de Reproducción y Desarrollo, Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. Av. Alameda B. O’Higgins 340, Santiago, Chile
    Unidad de Reproducción y Desarrollo, Departamento de Fisiología, Facultad de Ciencias Biológicas, Santiago, Pontificia Universidad Católica de Chile, Chile

    Fundación Médica San Cristóbal, Santiago, Chile
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  • Renán F. Orellana
    Unidad de Reproducción y Desarrollo, Departamento de Fisiología, Facultad de Ciencias Biológicas, Santiago, Pontificia Universidad Católica de Chile, Chile
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  • Manuel E. Cortés
    Unidad de Reproducción y Desarrollo, Departamento de Fisiología, Facultad de Ciencias Biológicas, Santiago, Pontificia Universidad Católica de Chile, Chile

    Departamento de Ciencias Animales, Facultad de Agronomía e Ingeniería Forestal, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Carmen T. Molina
    Unidad de Reproducción y Desarrollo, Departamento de Fisiología, Facultad de Ciencias Biológicas, Santiago, Pontificia Universidad Católica de Chile, Chile
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  • Barbara E. Switzer
    Florida State University College of Medicine, Tallahassee, Florida
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  • Hanna Klaus
    Natural Family Planning Center of Washington, DC, and Teen STAR Program, Bethesda, Maryland, USA
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Published:April 22, 2011DOI:


      Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.

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        • Schulz K.M.
        • Sisk C.L.
        Pubertal hormones, the adolescent brain, and the maturation of social behaviors: lessons from the Syrian hamster.
        Mol Cell Endocrinol. 2006; 254: 120
        • Walter L.
        • Miller D.M.S.
        Female puberty and its disorders.
        in: Yen S.C.C. Barbieri R. Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. W.B. Saunders Company, Philadelphia1999: 388-412
        • Santen R.J.
        The testis: Function and dysfunction.
        in: Yen S.S.C. Barbieri R. Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. W.B. Saunders Company, Philadelphia1999: 632-668
        • Vigil P.
        • Ceric F.
        • Cortés M.E.
        • et al.
        Usefulness of monitoring fertility from menarche.
        J Pediatr Adolesc Gynecol. 2006; 19: 173
        • García-Mayor R.V.
        • Andrade M.A.
        • Ríos M.
        • et al.
        Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage.
        J Clin Endocrinol Metab. 1997; 82: 2849
        • Sigel E.J.
        Adolescent growth and development.
        in: Greydanus D.E. Patel D.R. Pratt H.D. Essential adolescent medicine. McGraw Hill Professional, New York2005: 3-15
        • Spear L.
        Le développement du cerveau et les patterns de conduites typiques pendant l’adolescence (1re partie).
        Psychiatr Sci Hum Neurosci. 2008; 6: 149
        • Vigil P.
        La fertilidad de la pareja humana.
        Ediciones Universidad Católica de Chile, Santiago de Chile2004 (pp 47–62)
        • Martos-Moreno G.A.
        • Chowen J.A.
        • Argente J.
        Metabolic signals in human puberty: effects of over and undernutrition.
        Mol Cell Endocrinol. 2010; 324: 70
        • Ojeda S.R.
        • Dubay C.
        • Lomniczi A.
        • et al.
        Gene networks and the neuroendocrine regulation of puberty.
        Mol Cell Endocrinol. 2010; 324: 3
        • Roa J.
        • García-Galiano D.
        • Castellano J.M.
        • et al.
        Metabolic control of puberty onset: new players, new mechanisms.
        Mol Cell Endocrinol. 2010; 324: 87
        • Lerner R.
        • Steinberg L.
        Handbook of Adolescent Psychology.
        Wiley, New York2004 (pp 1–10)
        • Piaget J.
        Comments on Vygotsky’s critical remarks concerning “The language and thought of the child” and “Judgment and reasoning in the child”.
        MIT Press, Cambridge, Massachusetts1962 (pp 1–14)
        • Piaget J.
        Commentary on Vygotsky’s criticisms of language and thought of the child and judgment and reasoning in the child.
        New Ideas Psychol. 1995; 13: 325
        • Elkind D.
        Egocentrism in adolescence.
        Child Dev. 1967; 38: 1025
        • Goldman-Rakic P.S.
        • Chafee M.
        • Friedman H.
        Allocation of function in distributed circuits.
        in: Ono T. Squire L.R. Raichle M.E. Brain mechanisms of perception and memory: from neuron to behaviour. Oxford University Press, New York1993: 445-456
        • Luna B.
        The maturation of cognitive control and the adolescent brain.
        in: Aboitiz F. Cosmelli D. From attention to goal-directed behavior: neurodynamical, methodological and clinical trends. Springer-Verlag, Berlin Heidelberg2009: 249-267
        • Kail R.
        Processing time decreases globally at an exponential rate during childhood and adolescence.
        J Exp Child Psychol. 1993; 56: 254
        • Luna B.
        • Sweeney J.A.
        Cognitive development: fMRI studies.
        in: Keshavan M.S. Kennedy J.L. Murray R.M. Neurodevelopment and schizophrenia. Cambridge University Press, London/New York2004: 45-68
        • Yurgelun-Todd D.
        Emotional and cognitive changes during adolescence.
        Curr Opin Neurobiol. 2007; 17: 251
        • Casey B.J.
        • Giedd J.N.
        • Thomas K.M.
        Structural and functional brain development and its relation to cognitive development.
        Biol Psychol. 2000; 54: 241
        • Holm S.
        • Forbes E.
        • Ryan N.
        • et al.
        Reward-related brain function and sleep in pre/early pubertal and mid/late pubertal adolescents.
        J Adolesc Health. 2009; 45: 326
        • Masterman D.L.
        • Cummings J.L.
        Frontal-subcortical circuits: the anatomical basis of executive, social and motivational behaviors.
        J Psychopharmacol. 1997; 11: 107
        • Casey B.
        • Tottenham N.
        • Fossella J.
        Clinical, imaging, lesion, and genetic approaches toward a model of cognitive control.
        Dev Psychobiol. 2002; 40: 237
        • Galvan A.
        • Hare T.
        • Voss H.
        • et al.
        Risk-taking and the adolescent brain: who is at risk?.
        Dev Sci. 2007; 10: F8
        • Ernst M.
        • Bolla K.
        • Mouratidis M.
        • et al.
        Decision-making in a risk-taking task: a PET study.
        Neuropsychopharmacology. 2002; 26: 682
        • Casey B.J.
        • Jones R.M.
        • Hare T.A.
        The adolescent brain.
        Ann NY Acad Sci. 2008; 1124: 111
        • Farrant M.
        • Nusser Z.
        Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors.
        Nat Rev Neurosci. 2005; 6: 215
        • Shen H.
        • Gong Q.H.
        • Aoki C.
        • et al.
        Reversal of neurosteroid effects at α4β2δ GABAA receptors triggers anxiety at puberty.
        Nat Neurosci. 2007; 10: 469
        • McCarthy M.
        GABA receptors make teens resistant to input.
        Nat Neurosci. 2007; 10: 397
        • Andréen L.
        • Nyberg S.
        • Turkmen S.
        • et al.
        Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators.
        Psychoneuroendocrinology. 2009; 34: 1121
        • Sisk C.L.
        • Zehr J.L.
        Pubertal hormones organize the adolescent brain and behavior.
        Front Neuroendocrinol. 2005; 26: 163
        • Scott J.P.
        • Stewart J.M.
        • De Ghett V.J.
        Critical periods in the organization of systems.
        Dev Psychobiol. 1974; 7: 489
      1. Schulz KM, Zehr JL, Osetek AJ, et al: Exposure to gonadal hormones during puberty influences the cross-sectional area of the adult male ventromedial hypothalamus in response to estradiol and progesterone. In: Society for Neuroscience, Abstract Viewer/Itinerary Planner, Washington, DC, 2005

        • Bocklandt S.
        • Vilain E.
        Sex differences in brain and behavior: Hormones versus genes.
        Adv Genet. 2007; 59: 245
        • Phoenix C.H.
        • Goy R.W.
        • Gerall A.A.
        • et al.
        Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig.
        Endocrinol. 1959; 65: 369
        • Witelson S.
        Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study.
        Brain. 1989; 112: 799
        • Sperry R.
        Some effects of disconnecting the cerebral hemispheres.
        Science. 1982; 217: 1223
        • LaMantia A.
        • Rakic P.
        Cytological and quantitative characteristics of four cerebral commissures in the rhesus monkey.
        J Comp Neurol. 1990; 291: 520
        • Berrebi A.
        • Fitch R.
        • Ralphe D.
        • et al.
        Corpus callosum: region-specific effects of sex, early experience and age.
        Brain Res. 1988; 438: 216
        • Garcia-Falguerasa A.
        • Pinosa H.
        • Colladoa P.
        • et al.
        The role of the androgen receptor in CNS masculinisation.
        Brain Res. 2005; 1035: 13
        • de Vries G.J.
        • Simerly R.B.
        Anatomy, development, and function of sexually dimorphic neural circuits in the mammalian brain.
        in: Pfaff D. Arnold A. Etgen A. Hormones, brain and behavior. Elsevier, San Diego2002: 137-191
        • Giedd J.N.
        • Castellanos F.X.
        • Rajapakse J.C.
        • et al.
        Sexual dimorphism of the developing human brain.
        Prog Neuropsychopharmacol Biol Psychiatry. 1997; 21: 1185
        • Schlaepfer T.E.
        • Harris G.J.
        • Tien A.Y.
        • et al.
        Structural differences in the cerebral cortex of healthy female and male subjects: a magnetic resonance imaging study.
        Psychiatry Res. 1995; 61: 120
        • Bishop K.M.
        • Wahlsten D.
        Sex differences in the human corpus callosum: myth or reality?.
        Neurosci Biobehav Rev. 1997; 21: 581
        • Caviness V.S.
        • Kennedy D.N.
        • Richelme C.
        • et al.
        The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images.
        Cereb Cortex. 1996; 6: 726
        • de Blas M.R.
        • Segovia S.
        • Guillamón A.
        Effect of postpubertal gonadectomy on cell population of the locus coeruleus in the rat.
        Med Sci Res. 1990; 18: 355
        • Davis E.C.
        • Shryne J.E.
        • Gorski R.A.
        Structural sexual dimorphisms in the anteroventral periventricular nucleus of the rat hypothalamus are sensitive to gonadal steroids perinatally, but develop peripubertally.
        Neuroendocrinology. 1996; 63: 142
        • Frederikse M.E.
        • Lu A.
        • Aylward E.
        • et al.
        Sex differences in the inferior parietal lobule.
        Cereb Cortex. 1999; 9: 896
        • Nuñez J.L.
        • Sodhi J.
        • Juraska J.M.
        Ovarian hormones after postnatal day 20 reduce neuron number in the rat primary visual cortex.
        J Neurobiol. 2002; 52: 312
        • Guillamon S.
        • Segovia A.
        • Del Abril A.
        Early effects of gonadal steroids on the neuron number in the medial posterior region and the lateral division of the bed nucleus of the stria terminalis in the rat.
        Dev Brain Res. 1988; 44: 281
        • Gorski R.A.
        Critical role for the medial preoptic area in the sexual differentiation of the brain.
        Prog Brain Res. 1984; 61: 129
        • Forbes E.E.
        • Williamson D.E.
        • Ryan N.D.
        • et al.
        Positive and negative affect in depression: influence of sex and puberty.
        Ann N Y Acad Sci. 2004; 1012: 341
        • Giedd J.N.
        • Blumenthal J.
        • Jeffries N.O.
        • et al.
        Brain development during childhood and adolescence: a longitudinal MRI study.
        Nat Neurosci. 1999; 2: 861
        • Curry J.J.
        • Heim L.M.
        Brain myelinitation after neonatal administration of oestradiol.
        Nature. 1966; 209: 915
        • Jung-Testas I.
        • Renoir M.
        • Bugnard H.
        • et al.
        Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells.
        J Steroid Biochem Mol Biol. 1992; 41: 621
        • Kafitz K.W.
        • Herth G.
        • Bartsch U.
        • et al.
        Application of testosterone accelerates oligodendrocyte maturation in brains of zebra finches.
        Neuroreport. 1992; 3: 315
        • Brinton R.D.
        • Tran J.
        • Proffitt P.
        • et al.
        17 β-estradiol enhances the outgrowth and survival of neocortical neurons in culture.
        Neurochem Res. 1997; 22: 1339
        • Arai Y.
        • Sekine Y.
        • Murakami S.
        Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats.
        Neurosci Res. 1996; 25: 403
        • Diamond J.
        • Gray E.G.
        • Yasargil G.M.
        The function of dendritic spines: an analysis.
        J Physiol. 1969; 202: 116P
        • Coke B.M.
        • Wolley C.S.
        Gonadal hormone modulation of dendrites in the mammalian CNS.
        J Neurobiol. 2005; 64: 34
        • Chen J.R.
        • Yan Y.T.
        • Wang T.J.
        • et al.
        Gonadal hormones modulate the dendritic spine densities of primary cortical pyramidal neurons in adult female rat.
        Cereb Cortex. 2009; 19: 2719
        • Schulz K.M.
        • Richardson H.N.
        • Zehr J.L.
        • et al.
        Gonadal hormones masculinize and defeminize reproductive behaviors during puberty in the male Syrian hamster.
        Horm Behav. 2004; 45: 242
        • Hier D.B.
        • Crowley W.F.
        Spatial ability in androgen-deficient men.
        N Engl J Med. 1982; 306: 1202
        • Sherman M.R.
        • Corvol P.L.
        • O’Malley B.W.
        Progesterone-binding components of chick oviduct. I. Preliminary characterization of cytoplasmic components.
        J Biol Chem. 1970; 245: 6085
        • Jensen E.V.
        • DeSombre E.R.
        Estrogen-receptor interaction: Estrogenic hormones effect transformation of specific receptor proteins to a biochemically functional form.
        Science. 1973; 182: 126
        • Falkenstein E.
        • Wehling M.
        Nongenomically initiated steroid actions.
        Eur J Clin Invest. 2000; 30: 51
        • Luconi M.
        • Francavilla F.
        • Porazzi I.
        • et al.
        Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens.
        Steroids. 2004; 69: 553
        • Vigil P.
        • Orellana R.
        • Godoy A.
        • et al.
        Effects of gamma-amino butyric acid, progesterone and oestradiol on human spermatozoa acrosome reaction.
        in: Ballescà Lagarda J.L. Oliva Virgili R. Papers contributed to the 9th International Congress of Andrology. Medimond International Proceedings, Bologna2009: 107-111
        • Meizel S.
        The sperm, a neuron with a tail: ‘neuronal’ receptors in mammalian sperm.
        Biol Rev Camb Philos Soc. 2004; 79: 713
        • del Río M.J.
        • Godoy A.
        • Toro A.
        • et al.
        La reacción acrosómica del espermatozoide: avances recientes.
        Rev Int Androl. 2007; 5: 368
        • Weiner C.
        • Primeau M.
        • Ehrmann D.
        Androgens and mood dysfunction in women: comparison of women with polycystic ovarian syndrome to healthy controls.
        Psychosom Med. 2004; 66: 356
        • Goel N.
        • Bale T.L.
        Examining the intersection of sex and stress in modelling neuropsychiatric disorders.
        J Neuroendocrinol. 2009; 21: 415
        • Eriksson E.
        • Sundblad C.
        • Lisjö P.
        • et al.
        Serum levels of androgens are higher in women with premenstrual irritability and dysphoria than in controls.
        Psychoneuroendocrinology. 1992; 17: 195
        • Dalton M.E.
        Sex hormone-binding globulin concentrations in women with severe premenstrual syndrome.
        Postgrad Med J. 1981; 57: 560
        • Baischer W.
        • Koinig G.
        • Hartmann B.
        • et al.
        Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: elevated blood testosterone concentrations compared to normal controls.
        Psychoneuroendocrinology. 1995; 20: 553
        • Vogel W.
        • Klaiber E.L.
        • Broverman D.M.
        Roles of the gonadal steroid hormones in psychiatric depression in men and women.
        Prog Neuro-Psychopharmacol. 1978; 2: 487
        • Vigil P.
        • Cortés M.E.
        • del Río M.J.
        • et al.
        Síndrome de ovario poliquístico.
        in: Guzmán E. Lalonde A.B. Selección de temas en ginecoobstetricia, tomo II. Ediciones Publimpacto, Santiago de Chile2007: 561-578
        • Franks S.
        Polycystic ovary syndrome.
        N Engl J Med. 1995; 333: 853
        • Ibáñez L.
        • Potau N.
        • Ferrer A.
        • et al.
        Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidaemia, and subclinical hyperandrogenism.
        J Clin Endocrinol Metab. 2002; 87: 5702
        • Rasgon N.
        • Carter M.
        • Elman S.
        • et al.
        Common treatment of polycystic ovarian syndrome and major depressive disorder: case report and review.
        Curr Drug Targets Immune Endocr Metabol Disord. 2002; 2: 97
        • Ghaziuddin M.
        Polycystic ovary disease, manic-depressive illness and mental retardation.
        J Ment Defic Res. 1989; 33: 335
        • Orenstein H.
        • Raskind M.A.
        • Wyllie D.
        • et al.
        Polysymptomatic complaints and Briquet’s syndrome in polycystic ovary disease.
        Am J Psychiatry. 1986; 143: 768
        • Fontecilla A.
        • Worthington S.
        Análisis de la función de identidad en mujeres diagnosticadas con síndrome de ovario poliquístico a través del test de Rorschach.
        Tesis para optar al título profesional de Psicólogo, Universidad de Chile, Santiago2005