Library Selection 4 - Hormones and the Brain...some USA studies

Since October 30th, 2003

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Library Selection 1 - Kruijver et al,2000 and others Abstracts and Free Full Papers
Library Selection 2 - Aphallia & Sissyboys
Library Selection 3 - Transsexual Hormone Therapy (HRT)
Library Selection 4 - Hormones and the primate Brain... humans and non humans... USA studies.
Library Selection 5 - FtM Transsexual, Aphallia & Micropenis
Library Selection 6 - AR testosterone-DHT selectivity; Transgenders and Crossdressers
Library Selection 7 - AR testosterone-DHT selectivity; Torres & Jurberg Hypothesis
Library Selection 8 - SF-1 and DAX-1 papers
Library Selection 9 - Dörner....and the brain sexual differentiation
Library Selection 10 - Imperato_McGinley...and T action for the gender identity masculinization


See the so important papers from Roger Gorski and his team from UCLA, USA. He is very clear about the sex differention of the human brain... and about the primary femininity of all human (mammal) tissues...
1: Adv Exp Med Biol. 2002;511:57-70; discussion 70-3. Related Articles, Links

Hypothalamic imprinting by gonadal steroid hormones.

Gorski RA.

Department of Neurobiology, UCLA School of Medicine, Los Angeles, CA 90095, USA.

The results of more than four decades of research on different mammalian species have established that the brain, like the rest of the reproductive system, is esentially basically female. For the male to develop structural and functional characteristics typical of his species, his brain must be exposed to testicular hormones during a critical period, or critical periods, of development. As mammals, human beings are most likely subject to this process of the hormone-dependent sexual differentiation of the brain, but proving it will be difficult. Common sense ethics preclude experimental procedures such as castration of neonatal infants or exposing the female fetus to testosterone perinatally. Thus, scientists are restricted to the retrospective study of "Experiments of Nature." The results of such studies support to a degree a meaningful role of hormones in the development of the human brain. The concept of the sexual differentiation of brain structure and function has a potentially profound influence on clinical decisions with respect to sex assignment and clinical management of infants with ambiguous or poorly developed external genitalia. Because of the importance of a baby's sex in our culture, parents of such infants must be given consideration, but so should the infant whose hormonal environment prenatally may well have produced permanent changes in the structure and functional potential of his/her brain.

Publication Types:
  • Review
  • Review, Tutorial

PMID: 12575756 [PubMed - indexed for MEDLINE]
1: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7199-202. Related Articles, Links
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Sexual orientation and the size of the anterior commissure in the human brain.

Allen LS, Gorski RA.

Department of Anatomy and Cell Biology, University of California, Los Angeles 90024.

The anterior commissure, a fiber tract that is larger in its midsagittal area in women than in men, was examined in 90 postmortem brains from homosexual men, heterosexual men, and heterosexual women. The midsagittal plane of the anterior commissure in homosexual men was 18% larger than in heterosexual women and 34% larger than in heterosexual men. This anatomical difference, which correlates with gender and sexual orientation, may, in part, underlie differences in cognitive function and cerebral lateralization among homosexual men, heterosexual men, and heterosexual women. Moreover, this finding of a difference in a structure not known to be related to reproductive functions supports the hypothesis that factors operating early in development differentiate sexually dimorphic structures and functions of the brain, including the anterior commissure and sexual orientation, in a global fashion.

PMID: 1496013 [PubMed - indexed for MEDLINE]
1: Brain Res. 1992 May 8;579(2):321-6. Related Articles, Links

Sex differences in subregions of the medial nucleus of the amygdala and the bed nucleus of the stria terminalis of the rat.

Hines M, Allen LS, Gorski RA.

Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine 90024.

Sex differences are described in subregions of two nuclei of the rat brain: the medical nucleus of the amygdala (MA) and the bed nucleus of the stria terminalis (BNST). The volume of the posterodorsal region of the medial nucleus of the amygdala (MApd) is approximately 85% greater and the volume of the encapsulated region of the bed nucleus of the stria terminalis (BNSTenc) is approximately 97% greater in males than in females. The MApd and BNSTenc are distinct subregions of the MA and BNST. They exhibit intense uptake of gonadal hormones and are anatomically connected to each other and to other sexually dimorphic nuclei. The MA and BNST in general are involved in regulation of several sexually dimorphic functions, including aggression, sexual behavior, gonadotropin secretion and integration of olfactory information. Precise localization of sex differences in subregions of the MA and BNST, such as the MApd and BNSTenc, may facilitate understanding of the neural basis of such functions.

PMID: 1352729 [PubMed - indexed for MEDLINE]
1: J Comp Neurol. 1991 Oct 1;312(1):97-104. Related Articles, Links

Sexual dimorphism of the anterior commissure and massa intermedia of the human brain.

Allen LS, Gorski RA.

Department of Anatomy and Cell Biology, University of California, Los Angeles 90024.

Neuroanatomical sex differences were observed in the midsagittal area of both the anterior commissure and the massa intermedia on analysis of postmortem tissue from 100 age-matched male and female individuals. The anterior commissure, a fiber tract whose axons in primates primarily connect the two temporal lobes, was an average of 12%, or 1.17 mm2 larger in females than in males. The massa intermedia, a structure that crosses the third ventricle between the two thalami, was present in 78% of the females and 68% of the males. Among subjects with a massa intermedia, the structure was an average of 53.3% or 17.5 mm2 larger in females than in males. Inclusive of subjects with and without a massa intermedia, this structure was a mean of 76% or 16.93 mm2 greater in females than in males. These sex differences were present despite the fact that the brains of males were larger than those of females. Since a majority of subjects were adults, it is unknown when sexual differentiation occurred. Anatomical sex differences in structures that connect the two cerebral hemispheres may, in part, underlie functional sex differences in cognitive function and cerebral lateralization.

PMID: 1744245 [PubMed - indexed for MEDLINE]
1: J Neurosci. 1991 Apr;11(4):933-42. Related Articles, Links

Sex differences in the corpus callosum of the living human being.

Allen LS, Richey MF, Chai YM, Gorski RA.

Department of Anatomy and Cell Biology, University of California, Los Angeles 90024.

The sexual dimorphism of the corpus callosum has remained controversial since the original report by de Lacoste-Utamsing and Holloway in 1982, for several reasons: (1) measurements have been performed in a variety of ways in different laboratories, in part because published reports frequently do not describe the methodology in detail; (2) despite known age-related changes during both childhood and adulthood, no investigators have explicitly age-matched subjects; and (3) the size and shape of corpora callosa vary considerably among individuals, requiring large sample sizes to demonstrate significant sex differences. Therefore, we have examined magnetic resonance images for 24 age-matched children and 122 age-matched adults for possible sex differences in the corpus callosum. While we observed a dramatic sex difference in the shape of the corpus callosum, there was no conclusive evidence of sexual dimorphism in the area of the corpus callosum or its subdivisions. Utilizing several criteria, there were significant sex differences in shape: subjective evaluation indicated that the posterior region of the corpus callosum, the splenium, was more bulbous shaped in females as a group and in women, and more tubular-shaped in males as a group and in men; mathematical evaluation confirmed this observation in that the maximum width of the splenium was significantly greater in women than in men, and that the percentage by which the average width of the splenium was greater than that of the adjacent corpus callosum was significantly greater in females than in males. However, sex differences in bulbosity did not reach significance in children (aged 2-16 yr). In contrast, among the area measurements of the corpus callosum and 22 subdivisions, only 1 exhibited a significant sex difference, which would be expected by chance. The area of the corpora callosa increased significantly with age in children and decreased significantly with age in adults. In adults, the midsagittal surface area of the cerebral cortex decreased significantly with age in women but not in men. These anatomical sex differences could, in part, underlie gender-related differences in behavior and neuropsychological function.

PMID: 2010816 [PubMed - indexed for MEDLINE]
1: J Comp Neurol. 1990 Dec 22;302(4):697-706. Related Articles, Links

Sex difference in the bed nucleus of the stria terminalis of the human brain.

Allen LS, Gorski RA.

Department of Anatomy and Cell Biology, UCLA School of Medicine 90024.

A quantitative analysis of the volume of the darkly staining region of the posteromedial bed nucleus of the stria terminalis was performed on the brains of 26 age-matched male and female human subjects. We suggest the term "darkly staining posteromedial" component of the bed nucleus of the stria terminalis (BNST-dspm) to describe this sexually dimorphic region of the human brain. The volume of the BNST-dspm was 2.47 times greater in males than in females. This region in humans appears to correspond to an area of the bed nucleus of the stria terminalis in laboratory animals that exhibits volumetric and neurochemical sexual dimorphisms, concentrates gonadal steroids, and is anatomically connected to several other sexually dimorphic nuclei. Furthermore, the bed nucleus of the stria terminalis is involved in sexually dimorphic functions, including aggressive behavior, sexual behavior, and gonadotropin secretion, which are also influenced by gonadal steroids. Therefore, it is possible that in human beings as well, gonadal hormones influence the sexual dimorphism in the BNST-dspm and that this morphological difference, in part, underlies sexually dimorphic function.

PMID: 1707064 [PubMed - indexed for MEDLINE]
1: J Neurosci. 1989 Feb;9(2):497-506. Related Articles, Links

Two sexually dimorphic cell groups in the human brain.

Allen LS, Hines M, Shryne JE, Gorski RA.

Department of Anatomy, University of California, Los Angeles 90024.

A quantitative analysis of the volume of 4 cell groups in the preoptic-anterior hypothalamic area (PO-AHA) and of the supraoptic nucleus (SON) of the human brain was performed in 22 age-matched male and female individuals. We suggest the term Interstitial Nuclei of the Anterior Hypothalamus (INAH 1-4) to identify these 4 previously undescribed cell groups in the PO-AHA. While 2 INAH and the SON were not sexually dimorphic, gender-related differences were found in the other 2 cell groups. One nucleus (INAH-3) was 2.8 times larger in the male brain than in the female brain irrespective of age. The other cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the PO-AHA influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus may be related to sex differences in neural structure.

PMID: 2918374 [PubMed - indexed for MEDLINE]
Here we suggest you the studies in non human primates, developped in Portland by Resko & Roselli and others. We cannot study a lot of things in humans, but up until now we may study in non human primates.
1: Cell Mol Neurobiol. 1997 Dec;17(6):627-48. Related Articles, Links

Prenatal hormones organize sex differences of the neuroendocrine reproductive system: observations on guinea pigs and nonhuman primates.

Resko JA, Roselli CE.

Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97202-3098, USA.

1. The central nervous systems (CNS) of males and females differ in the control mechanisms for the release of gonadotropins from the anterior pituitary gland as well as the capacity to display sex specific behaviors. 2. In guinea pigs and monkeys, these differences are organized through the actions of prenatal androgens secreted by the fetal testes. In both males and females androgen receptors have been identified within the brain during the period in development in which organization of the CNS occurs. Sex differences between the ratio of cytosolic and nuclear androgen receptors are due to the amount of endogenous androgen present in the circulation of the developing fetus. Thus, at least part of the biochemical machinery necessary for androgen action resides in the CNS during the period of sexual differentiation. 3. In addition to the physiological differences that have been observed, morphological differences that are androgen dependent have been found in the medial preoptic nucleus and the bed nucleus of the stria terminalis of the guinea pig. The location of these sex differences in brain morphology coincides roughly with the location of steroid binding neurons. 4. In some species the in situ conversion of testosterone to dihydrotestosterone (DHT) by the 5 alpha-reductases or to estradiol-17 beta by cytochrome P450 aromatase mediates testosterone's action. The gonadotropin surge mechanism of adult guinea pigs exposed to a 5a-reductase inhibitor in utero during the critical period for sexual differentiation was unaffected in either males or females even though the development of the external organs of reproduction of males was feminized by the treatment. Likewise, the gonadotropin surge mechanism of subjects exposed to an aromatase inhibitor in utero during the critical period for sexual differentiation was unaffected by this treatment. 5. The mechanism controlling negative feedback, however, was affected in both males and females. Subjects that were exposed to an aromatase inhibitor while developing in utero could not respond to the negative feedback actions of estrogen on gonadotropin release in adulthood. 6. The surge mechanism for the control of gonadotropin secretion in nonhuman primates is not sexually differentiated as it is in rodents. Castrated male monkeys release surge amounts of LH in response to an estrogen challenge. Both infant and adult dimorphic behaviors of rhesus monkeys are organized by the prenatal actions of androgen.

Publication Types:
  • Review
  • Review, Tutorial

PMID: 9442350 [PubMed - indexed for MEDLINE]
1: Endocrine. 1998 Feb;8(1):51-60. Related Articles, Links

Immunocytochemical localization of androgen receptors in brains of developing and adult male rhesus monkeys.

Choate JV, Slayden OD, Resko JA.

Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098, USA.

We localized immunoreactive androgen receptors in the central nervous system (CNS) of fetal and adult male rhesus macaques by immunocytochemisty using an affinity-purified polyclonal antibody to the first 21 amino acids of the human androgen receptor (AR). This antibody caused a shift in the mobility of AR-bound 3H-DHT on a sucrose gradient and recognized a protein of approx 116 kDa on Western blot. Other criteria for specificity are presented. We localized AR in the diencephalon of male rhesus monkey fetuses. Immunoreactive neurons were found in the medial hypothalamic area and the ventromedial nucleus of the hypothalamus on days 47, 61, and 124 of gestation. At 124 d of gestation, AR immunoreactivity was aslo found in the arcuate nucleus. AR immunostaining was not found in other diencephalic structures in fetal life, including the preoptic area. In the adult monkey, neurons in ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus; cortical, medial, and accessory basal nuclei of the amygdala; and regions of the hippocampus and the anterior pituitary gland contained immunoreactive AR. These data indicate that AR is found in specific areas of the CNS early in fetal development, but they also appear in other brain areas as the fetus grows. At 124 d of gestation (term, 167 d), the hypothalamic location of immunoreactive AR is similar to the adult.

PMID: 9666345 [PubMed - indexed for MEDLINE]
1: Biol Reprod. 2000 Jun;62(6):1818-22. Related Articles, Links
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Region-specific regulation of cytochrome P450 aromatase messenger ribonucleic acid by androgen in brains of male rhesus monkeys.

Resko JA, Pereyra-Martinez AC, Stadelman HL, Roselli CE.

Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. reskoj@ohsu.edu

We demonstrated previously that testosterone regulates aromatase activity in the anterior/dorsolateral hypothalamus of male rhesus macaques. To determine the level of the androgen effect, we developed a ribonuclease protection assay to study the effects of testosterone or dihydrotestosterone (DHT) on aromatase (P450(AROM)) mRNA in selected brain areas. Adult male rhesus monkeys were treated with testosterone or DHT. Steroids in serum were quantified by RIA. Fourteen brain regions were analyzed for P450(AROM) mRNA. Significant elevations of its message over controls (P<0.05) were found in the medial preoptic area/anterior hypothalamus of both androgen treatment groups and the medial basal hypothalamus of the testosterone-treated males. Other brain areas were not affected by androgen treatment. We conclude that testosterone and DHT regulate P450(AROM) mRNA in brain regions that mediate reproductive behaviors and gonadotropin release. The P450(AROM) mRNA of other brain areas is not androgen dependent. Brain-derived estrogens may also be important for maintaining neural circuitry in brain areas not related to reproduction. The control of P450(AROM) mRNA in these areas may differ from what we report here, but it is equally important to understand the function of in situ estrogen formation in these areas.

PMID: 10819787 [PubMed - indexed for MEDLINE]
1: Biol Reprod. 2000 Sep;63(3):872-8. Related Articles, Links
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Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys.

Resko JA, Pereyra-Martinez AC, Stadelman HL, Roselli CE.

Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. reskoj@ohsu.edu

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.

PMID: 10952934 [PubMed - indexed for MEDLINE]
1: J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):247-53. Related Articles, Links
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Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance.

Roselli CE, Resko JA.

Department of Physiology and Pharmacology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA. rosellic@ohsu.edu

In adult male primates, estrogens play a role in both gonadotropin feedback and sexual behavior. Inhibition of aromatization in intact male monkeys acutely elevates serum levels of luteinizing hormone, an effect mediated, at least partially, within the brain. High levels of aromatase (CYP19) are present in the monkey brain and regulated by androgens in regions thought to be involved in the central regulation of reproduction. Androgens regulate aromatase pretranslationally and androgen receptor activation is correlated with the induction of aromatase activity. Aromatase and androgen receptor mRNAs display both unique and overlapping distributions within the hypothalamus and limbic system suggesting that androgens and androgen-derived estrogens regulate complimentary and interacting genes within many neural networks. Long-term castrated monkeys, like men, exhibit an estrogen-dependent neural deficit that could be an underlying cause of the insensitivity to testosterone that develops in states of chronic androgen deficiency. Future studies of in situ estrogen formation in brain in the primate model are important for understanding the importance of aromatase not only for reproduction, but also for neural functions such as memory and cognition that appear to be modulated by estrogens.

PMID: 11850231 [PubMed - indexed for MEDLINE]
See those important papers,from Donald Pfaff New York team, about ERKO rats (transgenic rats from who the ER alfa, or beta, or both, were knoked out). From them we may understand better the influence and importance of testosterone aromatization in the brain (hypothalamus and amygdalas mainly).
1: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14737-41. Related Articles, Links

Comment in: Click here to read 
Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO).

Ogawa S, Chester AE, Hewitt SC, Walker VR, Gustafsson JA, Smithies O, Korach KS, Pfaff DW.

Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021, USA. ogawa@rockvax.rockefeller.edu

Male mice with a knockout of the estrogen receptor (ER)-alpha gene, a ligand-activated transcription factor, showed reduced levels of intromissions and no ejaculations whereas simple mounting behavior was not affected. In contrast, all components of sexual behaviors were intact in male mice lacking the novel ER-beta gene. Here we measure the extent of phenotype in mice that lack both ER-alpha and ER-beta genes (alphabetaERKO). alphabetaERKO male mice did not show any components of sexual behaviors, including simple mounting behavior. Nor did they show ultrasonic vocalizations during behavioral tests with receptive female mice. On the other hand, reduced aggressive behaviors of alphabetaERKO mice mimicked those of single knockout mice of ER-alpha gene (alphaERKO). They showed reduced levels of lunge and bite aggression, but rarely showed offensive attacks. Thus, either one of the ERs is sufficient for the expression of simple mounting in male mice, indicating a redundancy in function. Offensive attacks, on the other hand, depend specifically on the ER-alpha gene. Different patterns of natural behaviors require different patterns of functions by ER genes.

PMID: 11114183 [PubMed - indexed for MEDLINE]
1: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12887-92. Related Articles, Links
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Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice.

Ogawa S, Chan J, Chester AE, Gustafsson JA, Korach KS, Pfaff DW.

Laboratory of Neurobiology, The Rockefeller University, New York, NY 10021, USA. ogawa@rockvax.rockefeller.edu

Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ERalpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ERbeta, demanded that we examine the possible participation of ERbeta in regulation of these behaviors. In dramatic contrast to our results with ERalpha knockout (alphaERKO) males, betaERKO males performed at least as well as wild-type controls in sexual behavior tests. Moreover, not only did betaERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience. These data revealed a significant interaction between genotype and social experience with respect to aggressive behavior. Finally, females lacking a functional beta isoform of the ER gene showed normal lordosis and courtship behaviors, extending in some cases beyond the day of behavioral estrus. These results highlight the importance of ERalpha for the normal expression of natural reproductive behaviors in both sexes and also provide a background for future studies evaluating ERbeta gene contributions to other, nonreproductive behaviors.

PMID: 10536018 [PubMed - indexed for MEDLINE]
1: Endocrinology. 1998 Dec;139(12):5070-81. Related Articles, Links
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Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice.

Ogawa S, Eng V, Taylor J, Lubahn DB, Korach KS, Pfaff DW.

Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, New York 10021, USA. ogawa@rockvax.rockefeller.edu

The role of gene expression of the estrogen receptor-alpha form (ER alpha) in the regulation of female reproductive behavior was investigated in estrogen receptor knockout (ERKO) mice, deficient specifically for the ER alpha, but not the ER beta, gene. Estrogen- or estrogen- plus progesterone-treated gonadectomized ERKO mice did not show any lordosis response. Detailed behavioral analysis revealed that ERKO females were also deficient in sexual behavioral interactions preceding the lordosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resident-intruder aggression tests, gonadally intact ERKO females were more aggressive toward female intruder mice than wild-type (WT) mice. Gonadectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gonadectomy. However, when mice were tested after gonadectomy for the first time, very few ERKO mice showed aggression. In contrast to aggression, male-type sexual behavior shown by resident mice toward female intruder mice during aggression tests was not different between ERKO and WT mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage. These changes in parental behavior were not influenced by gonadectomy. ERKO females retrieved significantly fewer numbers of pups with longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20-65 days after gonadectomy. In addition, during parental behavior tests, a significantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER alpha gene expression plays a key role in female mice, not only for sexual behavior but also for other interrelated behaviors, such as parental and aggressive behaviors. In addition, persistence of genotype differences in parental and aggressive behavior after gonadectomy indicates that ER alpha activation during neural developmental processes may also be involved in the regulation of these behaviors.

PMID: 9832446 [PubMed - indexed for MEDLINE]
1: Endocrinology. 1998 Dec;139(12):5058-69. Related Articles, Links
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Modifications of testosterone-dependent behaviors by estrogen receptor-alpha gene disruption in male mice.

Ogawa S, Washburn TF, Taylor J, Lubahn DB, Korach KS, Pfaff DW.

Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, New York 10021, USA. ogawa@rockvax.rockefeller.edu

The role of the a form of estrogen receptor (ER alpha) gene expression in the regulation of testosterone-dependent male reproductive behaviors was investigated using ER knockout mice (ERKO), which are specifically deficient in functional ER alpha, but not ER beta, gene expression. Previous studies in gonadally intact ERKO mice revealed that male aggressive behavior was greatly reduced by the lack of a functional ER alpha gene. In the present study the almost complete suppression of male-typical offensive attacks was further confirmed in ERKO mice that had been singly housed since weaning. Regarding aggression, it was also found that ER alpha gene disruption virtually abolished the propensity to initiate offensive attacks, even though ERKO mice could elicit attacks from resident C57BL/6J mice as wild-type (WT) and heterozygous littermates. Daily injection of testosterone propionate (TP) was completely ineffective in inducing aggressive behavior in gonadectomized ERKO mice, whereas it successfully restored aggression in WT mice. In contrast, male sexual behaviors, mounts and intromissions, were induced by daily injection of TP in both gonadectomized ERKO and WT mice. In addition to TP, dihydrotestosterone propionate (DHTP) was also effective in restoring mounts in ERKO mice, although DHTP was much more potent in WT mice than in ERKO mice. Neither TP nor DHTP, however, ever induced ejaculation in ERKO mice. These results together with previous findings in gonadally intact ERKO mice suggest that ER alpha may be responsible for the regulation by testosterone of consummatory, but not motivational, aspects of male sexual behavior. Finally, ERKO male mice retrieved newborn pups placed in their home cage with similar latencies to males of the two other genotypes. During parental behavior tests, however, a higher percentage of ERKO mice (70%) showed infanticide compared with WT mice (35%). The latter result was interpreted as showing that ER alpha activation by testosterone during the perinatal period may exert a suppressive effect on testosterone-inducible infanticide in adulthood. With respect to three major testosterone-dependent behavioral systems reflecting masculinization, these findings demonstrate three different types of effects due to ER alpha gene disruption.

PMID: 9832445 [PubMed - indexed for MEDLINE]
See here the important paper, where Sarah Newman, from Cornell University, proposes the existence of a SBN - a social behavior network in the brains of mammals (includding humans).
1: Ann N Y Acad Sci. 1999 Jun 29;877:242-57. Related Articles, Links
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The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network.

Newman SW.

Department of Psychology, Cornell University, Ithaca, New York 14853, USA. swn3@cornell.edu

Hormonal and chemosensory signals regulate social behaviors in a wide variety of mammals. In the male Syrian hamster, these signals are integrated in nuclei of the medial extended amygdala, where olfactory and vomeronasal system transmission is modulated by populations of androgen- and estrogen-sensitive neurons. Evidence from behavioral changes following lesions and from immediate early gene expression supports the hypothesis that the medial extended amygdala and medial preoptic area belong to a circuit that functions selectively in male sexual behavior. However, accumulated behavioral, neuroanatomical, and neuroendocrine data in hamsters, other rodents, and other mammals indicate that this circuit is embedded in a larger integrated network that controls not only male mating behavior, but female sexual behavior, parental behavior, and various forms of aggression. In this context, perhaps an individual animal's social responses can be more easily understood as a repertoire of closely interrelated, hormone-regulated behaviors, shaped by development and experience and modulated acutely by the environmental signals and the hormonal milieu of the brain.

Publication Types:
  • Review
  • Review, Academic

PMID: 10415653 [PubMed - indexed for MEDLINE]