A ROLE FOR OVARIAN HORMONES IN SEXUAL
DIFFERENTIATION OF THE BRAIN

<hr> Roslyn Holly Fitch  (1995) A Role for Ovarian Hormones in Sexual . Psycoloquy: 6(05) Sex Brain (1)<br>Versions: <a href=ftp://www.cogsci.soton.ac.uk/pub/psycoloquy//1995.volume.6/psyc.95.6.05.sex-brain.1.fitch>ASCII</a> <a href=http://www.cogsci.ecs.soton.ac.uk/cgi/psyc/newpsy?6.05>formatted</a><hr>
<TITLE>Psycoloquy 6(05): A Role for Ovarian Hormones in Sexual </TITLE>
<H1>A ROLE FOR OVARIAN HORMONES IN SEXUAL <br>
DIFFERENTIATION OF THE BRAIN<br>
</H1>
<ADDRESS>Roslyn Holly Fitch <br>
Center for Molecular and Behavioral Neuroscience<br>
Rutgers University <br>
197 University Ave. <br>
Newark, NJ  07102<br>
<br>
Victor H. Denenberg<br>
Biobehavioral Sciences Graduate Degree Program <br>
University of Connecticut <br>
Storrs, CT  06269-4154 <br>
<br>
<a href=mailto:holly@axon.rutgers.edu>holly@axon.rutgers.edu</a> 
<a href=mailto:dberg@uconnvm.uconn.edu>dberg@uconnvm.uconn.edu</a> 
</ADDRESS>
<P><H1>Abstract</H1><BLOCKQUOTE>
The role of endogenous hormones in differentiating the
sexes is an area of continuing research. The bulk of findings in
this field support the notion that mammalian sexual differentiation
is primarily mediated by androgens of testicular origin and that
the presence of these androgens in early life produces a "male"
brain. In contrast, the female brain is thought to develop via a
hormonal default mechanism, in the absence of androgen. Findings
are reviewed which show that ovarian hormones also play a
significant role in sexual differentiation, and that the process of
ovarian feminization has a considerably later sensitive period than
androgen-mediated masculinization.
</BLOCKQUOTE>
<P><H1>Keywords</H1><i>
corpus callosum, development, estrogen, feminization, 
ovaries, sensitive period. 
</i>
<H1>References</H1><UL>
<LI>Allen, L., Richey, M., Chai, Y. & Gorski, R. (1991) Sex differences in the cerebral cortex and the callosum of the living human being. Journal of Neuroscience 11; 933-942. 
<LI>Arnold, A.P. & Breedlove, S.M. (1985) Organizational and activational effects of sex steroids on brain and behavior: a reanalysis. Hormones and Behavior 19; 469-498. 
<LI>Barraclough, C.A. (1961) The production of annovulatory, sterile rats by single injections of testosterone priopionate. Endocrinology 68: 62-67. 
<LI>Bauer, R. (1978) Ontogeny of two-way avoidance in male and female rats. Developmental Psychobiology 11: 103-116. 
<LI>Becker, J.B. & Cha, J. (1989) Estrous-cycle variation in amphetamine induced behaviors and striatal dopamine release assessed with microdialysis. Behavioral Brain Research 35: 117-125. 
<LI>Bell, A.D. & Variend, S. (1985) Failure to demonstrate sexual dimorphism of the corpus callosum in childhood. Journal of Anatomy 143: 143-147. 
<LI>Berrebi, A.S., Fitch, R.H., Ralphe, D.L., Denenberg, J.O., Friedrich Jr., V.L. & Denenberg, V.H. (1988) Corpus callosum: region-specific effects of sex, early experience, and age. Brain Research 438: 216-224. 
<LI>Bleier, R., Houston, L. & Byne, W. (1986) Can the corpus callosum predict gender, age, handedness, or cognitive differences? Trends in Neuroscience 9: 391-394. 
<LI>Blizard, D. & Denef, C. (1973) Neonatal androgen effects on open-field activity and sexual behavior in the female rat: the modifying influence of ovarian secretions during development. Physiology and Behavior 11; 65-69. 
<LI>Bloch, G.J. & Gorski, R.A. (1988) Estrogen/progesterone treatment in adulthood affects the size of several components of the medial preoptic area in the male rat. Journal of Comparative Neurology 275: 613-622. 
<LI>Bloch, G.J. & Gorski, R.A. (1987) Estrogen treatment in adulthood affects the size of medial preoptic structures in the male rat. Society for Neuroscience Abstracts 13: 1165. 
<LI>Breedlove, S.M. (1992) Sexual differentiation of the brain and behavior. In Behavioral Endocrinology, J.B. Becker, S.M. Breedlove, and D. Crews, (Eds.) MIT Press, MA. p. 39-68. 
<LI>Breedlove, A.S. & Arnold, A.P. (1983) Hormonal control of a developing neuromuscular system II. Sensitive periods for the androgen-induced masculinization of the rat spinal nucleus of the bulbocavernosus. Journal of Neuroscience 3: 424-432. 
<LI>Byne, W., Bleier, R. & Houston, L. (1986) Individual, age and sex related differences in human corpus callosum: a study using magnetic resonance imaging. Society for Neuroscience Abstracts 12: 719. 
<LI>Camp, D., Robinson, T. & Becker, J. (1984) Sex differences in the effect of early experience on the development of behavioral and brain asymmetries in rats. Physiology and Behavior 33: 433-439. 
<LI>Castner, S.A. & Becker, J.B. (1990) Estrogen and striatal dopamine release: a microanalysis study. Society for Neuroscience Abstracts 16: 130. 
<LI>Clarke, S., Kraftsik, R., Van der Loos, H. & Innocenti, G.M. (1989) Forms and measures of adult and developing human corpus callosum: is there sexual dimorphism? Journal of Comparative Neurology 280: 213-230. 
<LI>Cowell, P.E., Allen, L.S., Zalatimo, N.S. & Denenberg, V.H. (1992) A developmental study of sex and age interactions in the human corpus callosum. Developmental Brain Research 66: 187-192. 
<LI>Davis, E.C., Elihu, N., Shryne, J.E. & Gorski, R.A. (1993) Evidence for post-pubertal onset of the volumetric sexual dimorphism and postpubertal growth of the anteroventral periventricular nucleus of the rat hypothalamus. Society for Neuroscience Abstracts 2: 1312. 
<LI>Dawson, J., Cheung, Y.M. & Lau, R.T.S. (1975) Developmental effects of neonatal sex hormones on spatial and activity skills in the white rat. Biological Psychology 3: 213-229. 
<LI>DeLacoste-Utamsing, C.M. & Holloway, R.L. (1982) Sexual dimorphism in the human corpus callosum. Science 216: 1431-1432. 
<LI>Demeter, S., Ringo, J. & Doty, R.W. (1985) Sexual dimorphism in the human corpus callosum? Society for Neuroscience Abstracts 11: 868. 
<LI>Denenberg, V.H. (1977) Assessing the effects of early experience. In Methods in Psychobiology, R.D. Myers. (Ed.) Academic Press. p. 127-147. 
<LI>Denenberg, V.H. (1981) Hemispheric laterality in animals and the effects of early experience. Behavioral and Brain Sciences 4: 1-49. 
<LI>Denenberg, V.H., Berrebi, A.S. & Fitch, R.H. (1989) A factor analysis of the rat's corpus callosum. Brain Research 497: 271-279. 
<LI>Denenberg, V.H., Brumaghim, J.T., Haltmeyer, G.C. & Zarrow, M.X. (1967) Increased adrenocortical activity in the neonatal rat following handling. Endocrinology 81: 1047-1052. 
<LI>Denenberg, V.H., Fitch, R.H., Schrott, L.M., Cowell, P.E. & Waters, N.S. (1991a) Corpus callosum: interactive effects of testosterone and handling in the rat. Behavioral Neuroscience 105: 562-566. 
<LI>Denenberg, V. H., Kertesz, A. & Cowell, P. E. (1991b) A factor analysis of the human's corpus callosum. Brain Research 548: 126-132. 
<LI>Denti, A. & Negroni, J. (1975) Activity and learning in neonatally hormone treated rats. Acta Physiologica Latinoamerica 25: 99-106. 
<LI>Diamond, M., Dowling, G. & Johnson, R. (1981) Morphologic cerebral cortical asymmetry in male and female rats. Experimental Neurology 71: 261-268. 
<LI>Diamond, M., Johnson, R.E. & Ehlert, J. (1979) A comparison of cortical thickness in male and female rats - normal and gonadectomized, young and adult. Behavioral Neurology 26: 485-491. 
<LI>Diamond, M., Johnson, R., Young, D. & Singh, S. (1983) Morphological hemispheric differences in the rat brain: male-female; right-left. Experimental Neurology 81: 1-13. 
<LI>Diaz-Veliz, G., Soto, V., Dussaubat, N. & Mora, S. (1989) Influence of the estrous cycle, ovariectomy and estradiol replacement upon the acquisition of conditioned avoidance responses in rats. Physiology and Behavior 46: 397-401. 
<LI>Dohler, K. (1991) The pre- and postnatal influence of hormones and neurotransmitters on sexual differentiation of the mammalian hypothalamus. International Reviews in Cytology 131: 1-57. 
<LI>Dohler, K.D., Hancke, J.L., Srivastava, S.S., Hofmann, C., Shryne, J.E. & Gorski, R.A. (1984a) Participation of estrogens in female sexual differentiation of the brain: neuroanatomical, neuroendocrine and behavioral evidence. In Progress in Brain Research, Vol. 61,  G.J. De Vries, J.P.C. De Bruin, H.B.M. Uylings, and M.A. Corner (Eds.) Elsevier Science Publishers. p. 99-117. 
<LI>Dohler, K.D., Srivasta, S., Shryne, J., Jarzab, B., Sipos, A. & Gorski, R.A. (1984b) Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is inhibited by postnatal treatment with an estrogen antagonist. Neuroendocrinology 38: 297-301. 
<LI>Fitch, R.H. Neonatal hormones and sexual dimorphism in the rat corpus callosum. 1990. Ph.D. dissertation, University of Connecticut. 
<LI>Fitch, R.H., Berrebi, A.S., Cowell, P.E., Schrott, L.M. & Denenberg, V.H. (1990a) Corpus callosum: effects of neonatal hormones on sexual dimorphism in the rat. Brain Research 515: 111-116. 
<LI>Fitch, R.H., Cowell, P.E., Schrott, L.M. & Denenberg, V.H. (1991a) Corpus callosum: perinatal anti-androgen and callosal demasculinization. International Journal of Developmental Neuroscience 9: 35-38. 
<LI>Fitch, R.H., Cowell, P.E., Schrott, L.M. & Denenberg, V.H. (1991b) Corpus callosum: ovarian hormones and feminization. Brain Research 542: 313-317. 
<LI>Fitch, R.H., Cowell, P.E., Schrott, L.S., & Denenberg, V.H. (1990b) Corpus callosum: neonatal hormones and development. Paper presented at the International Society for Developmental Psychobiology meeting, Cambridge, England. 
<LI>Fitch, R.H., Cowell, P.E., Schrott, L.M. & Denenberg, V.H. Failure to masculinize the corpus callosum with a non-aromatizable androgen. Ms in prep. 
<LI>Fitch, R.H., McGivern, R.F., Redei, E., Schrott, L.M., Cowell, P.E. & Denenberg, V.H. (1992) Neonatal ovariectomy and adrenal-pituitary responsiveness in the adult rat. Acta Endocrinologica 126: 44-48. 
<LI>Frankfurt, M., Gould, E., Woolley, C. S. & McEwen, B.S. (1990) Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: a golgi study in the adult rat. Neuroendocrinology 51: 530-535. 
<LI>Gerall, A., Dunlap, J. & Hendricks, S. (1973) Effects of ovarian secretions on female behavioral potentiality in the rat. Journal of Comparative and Physiological Psychology 82: 449-465. 
<LI>Gorski, R. (1984) Critical role for the medial preoptic area in the sexual differentiation of the brain. In Progress in Brain Research, Vol. 61, G.J. De Vries, J.P.C. De Bruin, H.B.M. Uylings, and M.A. Corner (Eds.) Elsevier Science Publishers. p. 129-145. 
<LI>Gould, F., Woolley, C.S., Frankfurt, M. & McEwen, B.S. (1990) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. Journal of Neuroscience 10: 1286-1291. 
<LI>Habib, M., Gayraud, D., Olivia, A., Regis, J., Salamon, G., & Khalil, R. (1991) Effects of handedness and sex on the morphology of the corpus callosum: A study with brain magnetic resonance imaging. Brain and Cognition 16: 41-61. 
<LI>Halpern, D.F. (1992) Sex Differences in Cognitive Abilities. Lawrence Erlbaum Associates, London. 
<LI>Hampson, E. (1990) Variations in sex-related cognitive abilities across the menstrual cycle. Brain and Cognition 14: 26-43. 
<LI>Hampson, E. & Kimura, D. (1988) Reciprocal effects of hormonal fluctuations on human motor and perceptual-spatial skills. Behavioral Neuroscience 102: 456-459. 
<LI>Hendricks, S.E. (1992) Role of estrogens and progestins in the development of female sexual behavior potential. In Handbook of Behavioral Neurobiology, vol. 11: Sexual Differentiation, A.A. Gerall, H. Moltz, and I.L. Ward (Eds.) Plenum Press, New York. p.129-155. 
<LI>Hines, M., Chiu, L., McAdams, L.A., Bentler, P.M. & Lipcamon, J. (1992) Cognition and the corpus callosum: verbal fluency, visuospatial ability, and language lateralization related to midsagittal surface areas of callosal subregions. Behavioral Neuroscience 106: 3-14. 
<LI>Juraska, J.M. & Kopcik, J.R. (1988) Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Research 450: 1-8. 
<LI>Kertesz, A., Polk, M., Howell, J. & Black, S. (1987) Cerebral dominance, sex, and callosal size in MRI. Neurology 37: 1385-1388. 
<LI>Kimura, D. (1987) Sex differences, human brain organization. In Encyclopedia of Neuroscience. Birkhauser Press, Boston. p. 1084-1085. 
<LI>Kimura, D. & Harshman, R. (1984) Sex differences in brain organization for verbal and non-verbal functions. In Progress in Brain Research, Vol. 61, G.J. De Vries, J.P.C. De Bruin, H.B.M. Uylings, and M.A. Corner (Eds.) Elsevier Science Publishers. p. 423-439. 
<LI>Krasnoff, A. & Weston, L. (1976) Puberal status and sex differences: activity and maze behavior in rats. Developmental Psychobiology 9: 261-269. 
<LI>Leret, M.L., Molina-Holgado, F. & Gonzales, M.I. (1994) The effect of perinatal exposure to estrogens on the sexually dimorphic response to novelty. Physiology and Behavior 55: 371-373. 
<LI>Lisk, R.D. & Suydam, A.J. (1967) Sexual behavior patterns in the prepubertally castrate rat. Anatomical Records 157: 181-189. 
<LI>Mack, C.M., Cowell, P.E. & Denenberg, V.H. (1992) Corpus callosum: interactive effects of handling and ovariectomy in the rat. Society for Neuroscience Abstracts 18: 213. 
<LI>Mack, C.M., Fitch, R.H. & Denenberg, V. (Submitted) Lack of activational influence of ovarian hormones on the size of the female rat's corpus callosum. 
<LI>Mack, C.M., Fitch, R.H., Cowell, P.E., Schrott, L.M. & Denenberg, V.H. (1993) Ovarian estrogen acts to feminize the rat's corpus callosum. Developmental Brain Research 71: 115-119. 
<LI>Masica, D.N., Money, J., Ehrhardt, A.A. & Lewis, V.G. (1969) IQ, fetal sex hormones, and cognitive patterns: studies of the testicular feminizing syndrome of androgen insensitivity. Johns Hopkins Medical Journal 124: 34-43. 
<LI>McCarthy, N.M., Schlenker, E.H. & Pfaff, D.W. (1993) Enduring consequences of neonatal treatment with antisense oligodeoxynucleotides to estrogen receptor messenger ribonucleic acid on sexual differentiation of rat brain. Endocrinology 133: 433-439. 
<LI>McCormick, C.M., Witelson, S.F. & Kingstone, E. (1990) Left-handedness in homosexual men and women: neuroendocrine implications. Psychoneuroendocrinology 15: 69-76. 
<LI>McGivern, R.F., Clancy, A.N., Hill, M.A. & Noble, E.P. (1988) Prenatal alcohol exposure alters adult expression of sexually dimorphic behavior in the rat. Science 224: 896-898. 
<LI>McGlone, J. (1980) Sex differences in human brain asymmetry: a critical survey. Behavioral and Brain Sciences 3: 215-263. 
<LI>Meaney, M.J., Aitken, D.H., Bhatnagar, S., Van Berkel, C. & Sapolsky, R.M. (1988) Postnatal handling attenuates neuroendocrine, anatomical, and cognitive impairments to the aged hippocampus. Science 238: 766-768. 
<LI>Miyakawa, M. & Arai, Y. (1987) Synaptic plasticity to estrogen in the lateral septum of the adult male and female rats. Brain Research 436: 184-188. 
<LI>Munoz-Cueto, J.A., Garcia-Segura, L.M. & Ruiz-Marcos, A. (1990) Developmental sex differences and effect of ovariectomy on the number of cortical pyramidal cell dendrite spines. Brain Research 515: 64-68. 
<LI>Nasrallah, H.A., Andreasen, N.C., Coffman, J.A., Olson, S.C., Dunn, V.D., Ehrhardt, J.C. & Chapman, S.M. (1986) A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia. Biological Psychiatry 21: 274-282. 
<LI>Oppenheim, J.S., Lee, B.C., Nass, R. & Gazzaniga, M.S. (1987) No sex-related differences in human corpus callosum based on magnetic resonance imagery. Annals of Neurology 21: 604-605. 
<LI>Pappas, C.T.E., Diamond, M.C. & Johnson, R.E. (1979) Morphological changes in the cerebral cortex of rats with altered levels of ovarian hormones. Behavioral and Neural Biology 26: 298-310. 
<LI>Resnick, S. & Berenbaum, S.A. (1982) Cognitive functioning in individuals with congenital hyperplasia. Behavioral Genetics 12: 594-595. 
<LI>Rhees, R.W., Shryne, J.E., & Gorski, R.A. (1990a) Onset of the hormone-sensitive perinatal period for sexual differentiation of the sexually dimorphic nucleus of the preoptic area. Journal of Neurobiology 21: 781-786. 
<LI>Rhees, R.W., Shryne, J.E., & Gorski, R.A. (1990b) Termination of the hormone-sensitive period for differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Developmental Brain Research 52: 17-23. 
<LI>Sodersten, P. (1976) Lordosis behavior in male, female, and androgenized female rats. Journal of Endocrinology 70: 409-420. 
<LI>Stewart, J. (1988) Current themes, theoretical issues, and preoccupations in the study of sexual differentiation and gender-related behaviors. Psychobiology 16: 315-320. 
<LI>Stewart, J. & Cygan, D. (1980) Ovarian hormones act early in development to feminize open field behavior in the rat. Hormones and Behavior 14: 20-32. 
<LI>Stewart, J. & Kolb, B. (1988) Asymmetry in the cerebral cortex of the rat: an analysis of the effects of neonatal gonadectomy on cortical thickness in three strains of rats. Behavioral and Neural Biology 49: 344-360. 
<LI>Toran-Allerand, D. (1992) Organotypic culture of the developing cerebral cortex and hypothalamus: relevance to sexual differentiation. In Psychoneuroendocrinology Vol. 16, P. Tallal and B. McEwen (Eds.) Pergamon Press, NY. p. 7-24. 
<LI>Toran-Allerand, D. (1986) Sexual differentiation of the brain. In Developmental Neuropsychology, W.T. Greenough, and J.M. Juraska (Eds.) Academic Press, London. p. 175-211. 
<LI>Wagner, C.K. & Clemens, L.G. (1989) Perinatal modification of a sexually dimorphic motor nucleus in the spinal cord of the B6D2F1 house mouse. Physiology and Behavior 45: 831-835. 
<LI>Ward, I. (1983) Effects of maternal stress on the sexual behavior of male offspring. Monographs in Neural Sciences, 9, 169-175. 
<LI>Whalen, R.F. & Edwards, D.A. (1967) Hormonal determinants of the development of masculine and feminine behavior in male and female rats. Anatomical Records 157: 173-180. 
<LI>Williams, C.L. (1986) A re-evaluation of the concept of separable periods of organizational and activational actions of estrogens in development of brain and behavior. Annals of the New York Academy of Sciences 474: 282-292. 
<LI>Witelson, S.F. (1991) Neural sexual mosaicism: sexual differentiation of the human tempero-parietal region for functional asymmetry. In Psychoneuroendocrinology, vol. 16, P. Tallal and B. McEwen (Eds.) Pergamon Press. p. 131-153. 
<LI>Witelson, S.F. (1989) Hand and sex differences in the isthmus and genu of the human corpus callosum. Brain 112: 799-835. 
<LI>Woolley, C.S., Gould, E., Frankfurt, M. & and McEwen, B.S. (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. Journal of Neuroscience, 10: 4035 - 4039. 
<LI>Zimmerberg, B. & Farley, M.J. (1993) Sex differences in anxiety behavior in rats: role of gonadal hormones. Physiology and Behavior 54: 1119-1124. 
<LI>Zimmerberg, B. & Mickus, L.A. (1990) Sex differences in corpus callosum: Influence of prenatal alcohol exposure and maternal undernutrition. Brain Research 537: 115-122. 
<LI>Zimmerberg, B. & Scalzi, L.V. (1989) Commissural size in neonatal rats: effects of sex and prenatal alcohol exposure. International Journal of Developmental Neuroscience 7: 81-86. 
</UL>