Male to Female Transsexual Individuals have Female Neuron Numbers in the Central Subdivision of the Bed Nucleus of the Stria Terminalis

MALE TO FEMALE TRANSSEXUAL INDIVIDUALS HAVE FEMALE NEURON NUMBERS IN THE CENTRAL SUBDIVISION OF THE BED NUCLEUS OF THE STRIA TERMINALIS

Dr Frank Kruijver, Dr Jiang-Ning Zhou, Dr Chris Pool, Dr Michel Hofman, Professor Louis Gooren & Professor Dick Swaab

Published in the Journal of Clinical Endocrinology & Metabolism, Vol 85. No: 5, 2034-2041 (2000)

SYNOPSIS

This study followed one similar piece of research on much of the same brain material, and was thus only the second of its kind to be done on human brains. The research team focussed on a part of the brain understood to be sexually dimorphic, the central subdivision of the bed-nucleus of the stria terminalis [BSTc]. The main neuron population of the BSTc is somatostatin-expressing [SOM] neurons.* The team sought to determine the number of SOM neurons in the BSTc [only those with visible nucleolus were counted], in relation to sex, sexual orientation, gender identity and past or present hormonal status.

42 human brains were collected in total: eight [8] gender dysphoric individuals, six [6] of whom were male-to-female individuals ( MtF, transwomen) and had undergone transition, including hormone treatment and surgery, one [1] male-to-female individual who had undergone no treatment whatever, but who had always strongly identified as female, and one [1] female-to-male individual (FtM, transman).

The control group of 34 individuals included: nine [9] homosexual men, nine [9] heterosexual men, ten [10] presumed heterosexual women, three [3] women with hormone disorders, three [3] men with hormone disorders.

The findings indicated that, regardless of sexual orientation, men had almost twice as many SOM neurons as women (P< 0.006). The number of SOM neurons in the BSTc of the transwomen [MtF] was similar to the other women (P= 0.83). In contrast, the neuron number of a transman [FtM] was found to be in the male range. Hormone treatment or sex hormone level variations in adulthood seemed to have no impact on BSTc neuron numbers. The relative volumes of the BSTc were also measured. All of the men, regardless of sexual orientation, had volumes which were similar; the women and the transwomen [MtF] had similar volumes; the transman [FtM] fell into the same range as the other men. The volumes of all men versus all women and transwomen [MtF] were statistically highly significant (P< 0.01)

No statistical differences were found for age, post-mortem time, fixation time, storage time or cause of death, nor were any differences found between early, rather than late, recognition of gender dysphoria/transsexualism. The effects of variations in levels of estrogen, testosterone, antiandrogen treatments and orchidectomy were also tested and appeared to have no effect on the BSTc.

The finding of SOM neuronal sex differences in the BSTc and the sex reversal of these differences in the brains of gender dysphoric individuals, clearly supports the paradigm that in these individuals, the sex differentiation of the brain and the genitals may go in opposite directions. This points to a neurobiological basis, established during early development, for the condition of gender dysphoria.

*somatostatin is a polypeptide hormone, produced in the brain (and also the pancreas), which appears to inhibit the secretion of other hormones.

References

1. MacLusky NJ, Naftolin F. 1981 Sexual differentiation of the central nervous system. Science. 211:1294-1302. [Medline] 2. Kawata M. 1995 Roles of steroid hormones and their receptors in structural organization in the nervous system. Neurosci Res. 24:1-46. [Medline] 3. Allen LS, Gorski RA. 1990 Sex difference in the bed nucleus of the stria terminalis of the human brain. J Comp Neurol. 302:697-706. [Medline] 4. Swaab DF, Hofman MA. 1990 An enlarged suprachiasmatic nucleus in homosexual men.
Brain Res. 537:141-148.[Medline] 5. LeVav S. 1991 A difference in hypothalamic structure between heterosexual and homosexual men. Science. 253:1034-1037. [Medline] 6. Allen L,S, Gorski RA. 1992 Sexual orientation and the size of the anterior commissure in the human brain. Proc Natl Acad Sci USA. 89:7199-7202. [Abstract] 7. Swaab DF, Hofman MA. 1995 Sexual differentiation of the human hypothalamus in relation to gender and sexual orientation. Trends Neurosci- 18:264-270. [Medline] 8. Swaab DF, Fliers E. 1985 A sexually dimorphic nucleus in the human brain. Science. 228:1112-1115. [Medline] 9. Miller BL, Cummings JL, Mclntyre H, Ebers G. Grode M. 1986 Hypersexuality or altered sexual preference following brain injury. J Neurol Neurosurg Psychiatry. 49:867- 873.[Abstract] 10. Gorman DG, Cummings JL. 1992 Hypersexuality following septal injury.
Arch Neurol. 49:308-310. [Medline] 11. Beyer C, Hutchison JB. 1997 Androgens stimulate the morphological maturation of embryonic hypothalamic aromatase-immunoreactive neurons in the mouse. Brain Res Dev Brain Res. 98:74--81.[Medline] 12. Swaab DF, Slob AK. Houtsmuller EJ, Brand T, Zhou JN. 1995 Increased number of
vasopressin neurons in the suprachiasmatic nucleus (SCN) of "bisexual" adult male rats
Brain Res Dev Brain Res. 85:273-279. [Medline] 13. Liu YC, Salamone JD, Sachs BD. 1997 Lesions in medial preoptic area and bed nucleus of stria terminalis: differential effects on copulatory behavior and noncontact erection in male rats. J Neurosci. 17:5245-5253. [Abstract/Full Text] 14. Herbison AE, Theodosis DT. 1993 Absence of estrogen receptor immunoreactivity in somatostatin (SRIF) neurons of the periventricular nucleus but sexually dimorphic colocalization of estrogen receptor and SRIF immunoreactivities in neurons of the bed nucleus of the stria terminalis. Endocrinology. 132:1707-1714.[Abstract]
15. McEwen BS, Alves SE, Bulloch K, Weiland NG. 1997 Ovarian steroids and the brain: implications for cognition and aging. Neurology. 48 (Suppl 7).
16. Pfaff DW. 1997 Hormones, genes, and behavior. Proc Natl Acad Sci USA. 94:14213-
14216. [Abstract/Full Text] 17. Simonian SX, Murray HE, Gillies GE, Herbison AE. 1998 Estrogen-dependent ontogeny of sex differences in somatostatin neurons of the hypothalamic periventricular nucleus. Endocrinology. 139:1420-1428. [Abstract/Full Text]
18. McEwen BS. 1999 The molecular and neuroanatomical basis for estrogen effects in the central
nervous system. J Clin Endocrinol Metab. 84:1790-1797. [Full Text]
19. Gooren L.J. 1990 The endocrinology of transsexualism: a review and commentary. Psychoneuroendocrinology. 15:3-14. [Medline] 20. Editorials. 1991 Transsexualism. Lancet. 338.603-604.[Medline] 21. Bradley SJ, Zucker KJ. 1997 Gender identity disorder: a review of the past 10 years.
J Am Acad Child Adolesc Psychiatry. 36:872-880. [Medline] 22. Zhou JN, Hofman MA, Gooren LJ. Swaab DF. 1995 A sex difference in the human brain and its relation to transsexuality. Nature. 378:68-70. [Medline] 23. Walter A, Mai JK, Lanta L, Gores T. 1991 Differential distribution of immunohistochemical markers in the bed nucleus of the stria terminalis in the human brain.
J Chem Neuroanat. 4:281-298. [Medline] 24. Shi SR, Cote RJ, Taylor CR. 1997 Antigen retrieval immunohistochemistry: past, present, and future. J Histochem Cytochem. 45:327-343.[Abstract/Full Text]
25. van de Nes JA, Kamphorst W, Ravid R, Swaab DF. 1993 The distribution of Alz-50 immunoreactivity in the hypothalamus and adjoining areas of Alzheimer's disease patients. Brain. 116:103-115. [Abstract] 26. Gundersen HJG. 1977 Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J Microsc. 111:219-223. 27. Zhou JN, Hofman MA, Swaab DF. 1996 Morphometric analysis of vasopressin and vasoactive intestinal polypeptide neurons in the human suprachiasmatic nucleus: influence of microwave treatment. Brain Res. 742:334-338. [Medline]
28. Bennett PA, Levy A, Carmignac DF, Robinson IC, Lightman SL. 1996 Differential
regulation of the growth hormone receptor gene: effects of dexamethasone and estradiol. Endocrinology. 137-3891-3896. [Abstract] 29. Chowen JA, Argente J, Gonzalez-Parra S, Garcia-Segura LM. 1993 Differential effects of the neonatal and adult sex steroid environments on the organization and activation of hypothalamic growth hormone-releasing hormone and somatostatin neurons. Endocrinology. 133:2792-2802.[Abstract] 30. Cohen-Kettenis PT, van Goozen SHM, Doorn CD, Gooren LJG. 1998 Cognitive ability and cerebral lateralisation in transsexuals. Psychoneuroendocrinology. 23:631- 641. [Medline] 31. Del Abril A, Segovia S, Guillamon A. 1987 The bed nucleus of the stria terminalis in the rat: regional sex differences controlled by gonadal steroids early after birth. Brain Res. 429:295-300. [Medline]
32. Guillamon A, Segovia S, Del Abril A. 1988 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 terrninalis in the rat. Brain Res Dev Brain Res. 44:281-290.[Medline]
33. Breedlove SM, Arnold AP. 1981 Sexually dimorphic motor nucleus in the rat lumbar spinal cord: response to adult hormone manipulation, absence in androgen-insensitive rats.
Brain Res. 25:297-307. 34. Breedlove SM. 1997 Sex on the brain. Nature. 389:801.
35. Mayer A, Lahr G, Swaab DF, Pilgrim C, Reisert I. 1998 The Y-chromosomal genes SRY and ZFY are transcribed in adult human brain. Neurogenetics. 1:281-288. [Medline]
36. Collaer ML, Hines M. 1995 Human behavioral sex differences: a role for gonadal hormones
during early development? Psychol Bull. 118:55-107.[Medline] 37. Reiner WG. 1996 Case study: sex reassignment in a teenage girl. J Am Acad Child Adolesc Psychiatry. 35:799-803. [Medline] 38. Meyer-Bahlburg HF, Gruen RS, New MI, et al. 1996 Gender change from female to male in classical congenital adrenal hyperplasia. Horm Behav. 30:319-332. [Medline]
39. Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, v d Poll N, Koppe JG. 1999 Prenatal
exposure to anticonvulsants and psychosexual development.Arch Sex Behav. 28:3 I- 44.[Medline]
40. Diamond M, Sigmundson HK. 1997 Sex reassignment at birth. Long-term review and clinical implications. Arch Pediatr Adolesc Med. 151:298-304. [Medline] 41. de Courten-Myers G. 1999 The human cerebral cortex: gender differences in structure and function. J Neuropathol Exp Neurol. 158:217-226.

win XP / 98 tips | win XP security | 10 ways to pay for SRS | what is transgender? | photo portfolio