Dieser Tweet hier wies mich auf eine interessante Studie hin:
Bisher war ich von dem Modell ausgegangen, dass ein niedriger Stand an pränatalen Testosteron eher mit Homosexualität in Verbindung steht. Aber anscheinend kann auch ein sehr hoher Stand an pränatalen Testosteron dazu führen.
Aus der Studie:
Dannach wären also Homosexuelle, die eher „weiblicher“ sind durch weniger Testosteron entstanden, Homosexuelle, die eher „Männlicher“ sind durch eine „Überdosis“ Testosteron. Und anscheinend geht die Unterscheidung „Bottom“ und „top“ da mit. Was auch interessant wäre.
Aus der Studie:
Homosexualität und Testosterone
Da wären also die verschiedensten Veränderungen und ihre Auswirkungen dargelegt. Von Testosteronständen über Östrogenrezeptoren (das Testosteron wird ja vor der Wirkung im Gehirn in Östrogen umgewandelt, bestimmten Knockout-Varianten etc.
Aus der Studie:
Hormone manipulation studies were the first line of evidence to suggest that androgen action during early development organize the brain and behavior in a sex-typical fashion. Females exposed to androgens during early critical periods display male-typical sexual behaviors in adulthood; Phoenix et al. (1959), first reported these findings in guinea pigs, and many others have replicated these findings in mice and
rats (for review, see Cooke et al., 1998). In male rodents, removal of gonadal androgens during early development (e.g., Gerall et al., 1967), or prenatal and postnatal treatment with anti-androgens (e.g., flutamide: Clemens et al., 1978; Casto et al., 2003; cyproterone acetate:Ward and Renz, 1972), results in dramatic decreases in male-typical sexual behaviors (i.e., decreased mounting, intromissions and ejaculation), and increased female-typical behaviors such as lordosis (e.g., Gladue and Clemens, 1978; Ward and Renz, 1972) when treated with hormone regimens that typically induce receptivity in females (i.e., estradiol and progesterone). Similarly, sexual preferences, as measured by simultaneous exposure to male and female partner or sexual odor stimuli, are mediated by androgens: male-typical levels of androgen exposure during early development increases preference for female sexual stimuli, whereas the absence of or low-level androgen exposure leads to a preference for male sexual stimuli (e.g., Domınguez-Salazar et al., 2002; Stern, 1970). Together, such studies suggest that low level androgen exposure during development results in female-typical sexual behaviors and preferences, while higher male-typical androgen levels promote male-typical sexual behaviors and preferences in adult mice and rats (see Table 1).
Das ist ein guter Überblick über die verschiedensten Studien auf dem Gebiet, die das für Tiere entsprechend nachweisen.
There are a couple caveats to consider when evaluating these early androgen manipulation studies; for one, androgens can act via both androgenic and estrogenic signaling pathways. Testosterone, the primary
androgen produced by the gonads, can be metabolized into either the more potent androgen dihydrotestosterone (DHT) or, with the help of the enzyme aromatase, converted to estrogens (Naftolin, 1994; reviewed in Roselli et al., 2009). Thus, it is difficult to parse out the effects of androgen action via the androgen receptor (AR) versus the estrogen receptors (ERs). Many studies have manipulated estrogens and the enzyme aromatase to assess estrogenic effects on behavior; indeed, such studies have indicated that androgen action via ERs contributes to the display of male-typical sexual behavior and sexual preferences (e.g., Brand et al., 1991; Clemens and Gladue, 1978; for review in rats, see Bakker et al., 1996; in mice, see Bodo, 2008; Brock and Bakker, 2011; for review comparing mice and rats, see Bonthuis et al., 2010). However, a second limitation of androgen or estrogen manipulation studies is that simply manipulating circulating hormones may not alter hormone levels in the brain; for example, removal of both gonadal and adrenal hormones at birth does not seem to alter the neural endocrine environment, even 3 days following gonad and adrenal removal (Konkle and McCarthy, 2011); these findings could be accounted for by de novo steroid synthesis in the brain (Robel and Baulieu, 1995; reviewed in Diotel et al., 2018 and Forger et al., 2016). Neural hormone implantations were first to address the role of hormones directly in the brain for behavior (e.g., Davidson, 1966; for review see McEwen et al., 1979; Frye, 2001), and modern transgenic technology (and spontaneous mutations of the androgen receptor gene) has allowed for the refined testing of the effects of androgenic signaling compared to estrogenic signaling on sexual behaviors by targeting hormone receptors.
With transgenic mouse models, we can ensure hormone sensitivity is altered specifically in neural tissue, even if hormone synthesis continues in the brain following gonadectomy. Prior to modern transgenic technology, Lyon and Hawkes (1970) described the condition of testicular feminization mutation (Tfm) in mice, in which XY chromosomal male mice showed a female phenotype at birth. It was later discovered that these rodents have a single nucleotide deletion in the androgen receptor gene, causing a frameshift mutation that renders AR nonfunctional (Charest et al., 1991). Males with this mutation present as females in their somatic features, having a smaller anogenital distance, blind vaginal canal, nipples and a reduced body weight, falling within the female-typical range. Their behavior is also more female-typical, such that they are demasculinized in sexual behaviors such as mounting (reviewed in Zuloaga et al., 2008). Tfm
male mice also exhibit a female-typical preference for male sexual stimuli
and show a female-typical pattern of neural activity in response to same-sex odors, even when treated with exogenous estrogens (Bodo and Rissman, 2007). Together these findings suggest AR is necessary for male-typical behaviors and sexual preferences, and the lack of androgenic signaling increases female-typical sexual preferences. Subsequent studies indicated that the lack of functioning AR affects estrogenic signaling (Bodo and Rissman, 2007), and there is some evidence for non-classical effects of AR or a novel/yet-to-be identified AR that may be functional in Tfm male mice (Tejada and Rissman, 2012). Nevertheless, the Tfm mouse model has been valuable in studying the role of classical AR function, and provides evidence for a role of AR in male sexual behaviors and preferences (reviewed in Zuloaga et al., 2008; Swift-Gallant and Monks, 2017).
With modern transgenic technology, mouse models are now available with AR knocked-out either globally or selectively in neural tissue, allowing for a more refined understanding of the role of AR for maletypical
sexual behaviors and preferences. Results from global AR knockout (KO) models largely recapitulate the finding from the Tfm mouse literature. For example, Sato et al. (2004) found that male mice with complete AR-KO did not display male-typical sexual behaviors
including mounting, intromissions and ejaculation; estradiol administration
was partially successful in restoring mounting and intromissions in these mice, but not ejaculation. Similarly, neural-only AR-KO resulted in decreased male sexual behaviors (Juntti et al., 2010; Raskin et al., 2009), although not to the extent found with complete loss of AR function. Furthermore, sexual odor preferences were reported to be undisturbed in neural-only AR-KO males (Raskin et al., 2009), whereas Tfm male mice with complete AR insensitivity displayed a sex-reversal in this behavior. These results support a role for androgens via AR for male sexual behaviors, although KO of neural AR alone is insufficient to affect sexual preferences, suggesting non-neural AR plays a role in sexual preferences in mice (reviewed in Swift-Gallant and Monks, 2017). Although, Chen et al. (2015) raise the concern that AR is not completely knocked-out in the brain of the Nestin-AR KO mouse model, and thus it is possible that residual AR expression could continue to masculinize some aspects of behavior.
The influences of both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) have also been tested using mouse KO models. With ERα-KO, male mice exhibit decreases in male-typical sexual behaviors, although testosterone and DHT are both able to induce mounts and intromissions in ERα-KO males, but not ejaculation (Ogawa et al., 1998). Interest in investigating female partners is also decreased in ERα-KO male mice, although they continue to show increased neural activation in response to female odors, similar to wildtype males, and they exhibit the expected surge in luteinizing hormone in response to opposite-sex odors (Wersinger and Rissman, 2000). On the other hand, while ERβ-KO males continue to show male-typical sexual behaviors and a preference for female sexual stimuli, they exhibit a higher propensity for female-typical sexual behaviors such as lordosis when primed with estrus-inducing hormones when compared with wildtype male mice (Kudwa et al., 2005). Together, these results suggest ERα is required for masculinization of male sexual behaviors, while ERβ is responsible for the defeminization of sexual behavior in male mice (reviewed in Kudwa et al., 2006).
Similar conclusions have been drawn from studying alpha-feto protein (AFP) and aromatase KO mouse models. AFP in embryonic females restricts maternal estrogens from entering the central nervous system (CNS) and masculinizing neural structure (McEwen et al., 1975). Thus, sans AFP, maternal estrogens can enter the developing brain in female offspring and masculinize neural development. Indeed, AFP-KO females exhibited male-typical sexual behaviors and not female-typical sexual behaviors in adulthood, suggesting maternal estrogens are sufficient to masculinize and defeminize the female CNS and behavior in the absence of AFP (Bakker et al., 2006). However, sexual preference for female sexual stimuli is not masculinized in AFPKO females (Bakker et al., 2007), supporting a role for androgen action via AR for male-typical sexual preferences (reviewed in Forger et al., 2016).
Without aromatase, androgens can only act directly via AR because they cannot be metabolized to estradiol to act via ERs. Interestingly, male aromatase KO mice display dramatic decreases in male-typical sexual behaviors (i.e., mounting of receptive females; Honda et al., 1998) and they show a decreased preference for female odor stimuli (Bakker et al., 2002), suggesting that aromatization of testosterone to estradiol is necessary for these behaviors. However, aromatase KO males continue to show similar patterns of neural activation in response to opposite and same-sex odors to wildtype males (Pierman et al., 2008), suggesting that the male-typical neural response to opposite-sex odor stimuli depends on androgen action via AR. Together, the evidence suggests that androgens act via both AR and ERs to promote male-typical sexual behavior and inhibit female-typical sexual behavior. All knockout models interrupting the ability for androgens to act via AR or ERα drastically alter male-typical behaviors such as mounting, intromissions and ejaculation. ERβ, on the other hand, is required for the defeminization of behaviors such as lordosis, and AR is uniquely required for male sexual odor preferences and corresponding neural activity in response to sexual odor stimuli
Ich habe diesen längeren Text hier einmal zitiert, weil er auf das komplexe Zusammenspiel vieler biologischer Faktoren hinweist und auch deutlich macht, dass auch die Erforschung der Zusammenhänge nicht so einfach ist, auch wenn sich aus den gesammelten Ergebnissen ein recht deutliches Bild ergibt. Die Auflistung der vielen verschiedenen Besonderheiten macht deutlich, dass es ganz verschiedene Wege in dem System gibt, wie Homosexualität entstehen kann. Es macht aber auch deutlich, dass Sexuelle Orientierung und Verhalten eine deutliche biologische Komponente haben
Und zu dem stark erhöhten Testosteronstand:
At least 6 studies have evaluated the effects of elevated androgen exposure during early critical periods in development on the display of adult male sexual behavior and/or preferences in rodents (Diamond et al., 1973; Piacsek and Hostetter, 1984; Zadina et al., 1979; Henley et al., 2010; Cruz and Pereira, 2012). Overall, these studies suggest that exogenous androgen treatment during early development increases preference for same-sex partners in male rodents. For example, Henley et al. (2010) found that sexual behaviors were reduced in response to female conspecifics among male rats exposed to supraphysiological levels of testosterone during early postnatal development (i.e., day of birth-postnatal day 21). Instead, these hyperandrogenized male rats exhibited an increase interest in investigating male partners compared to unmanipulated male rats that preferred female partners. Similarly, Cruz and Pereira (2012) found that male rats administered testosterone between embryonic days 17–19 (i.e., administered to pregnant dams; coinciding with the endogenous spike in androgens in unmanipulated male rats), showed a decrease preference for female partners and increased preference for male partners compared to control male rats. Collectively, androgen manipulation studies indicate that at the high extent of androgen signaling male-typical sexual behaviors persist, but male-typical preferences are altered, such that male rodents show increased androphilic sexual preference. The role of higher androgen signaling via AR was recently tested with modern transgenic technology. When AR is overexpressed in male mice to levels 3–4× higher than in wildtype counterparts, male mice continued to exhibit male-typical sexual behaviors while androphilic sexual preferences were increased (Swift-Gallant et al., 2016a, 2016b). Specifically, using cre-loxP system, two models of AR overexpression were created, one with global overexpression and a second with neuralspecific overexpression of AR. Swift-Gallant et al. (2016a) found that male mice with global AR overexpression exhibited an increase in maletypical sexual behaviors (e.g., number of thrusts/mount) in response to a receptive female partner. While these males continued to show sexual interest in female partners, males with global overexpression showed a greater preference for the anogenital investigation of male partners and a decrease in aggressive behaviors towards male intruders (SwiftGallant et al., 2016a). Moreover, male mice with global AR overexpression show a greater preference for male odors when presented simultaneously with male and female odor stimuli (Swift-Gallant et al., 2016b). Neural activity in response to female odors along the accessory olfactory pathway was also decreased in male mice with global AR overexpression compared to control males, corresponding with the behavioral results (Swift-Gallant et al., 2016b). Conversely, male mice with neural-only AR overexpression (Nestin-AR; Swift-Gallant et al., 2016a, 2016b) did not exhibit differences in sexual behavior or sexual preferences compared to wildtype males, though these mice did display a dramatic decrease in inter-male aggression. Together, these results suggest that global increases in androgenic signaling promote androphilic sexual preferences and male-typical sexual behaviors in male mice, whereas neural-only increases in AR were insufficient to alter these behaviors. The literature to date suggests that at the high end of androgen signaling androphilic sexual preferences are increased, while male-typical sexual behaviors (i.e., mounting, thrusting) remain intact. In other words, male rodents treated with exogenous androgens or with global increases in AR signaling continue to perform the same sexual behaviors as wildtype males (i.e., mounting/thrusting), but these hyperandrogenized males exhibit an increased preference for same-sex partners and sexual stimuli. However, there remain questions for future research to address: namely, in some studies hyperandrogenization decreased preference for female partners while increasing androphilia (e.g., Cruz and Pereira, 2012), while in other studies preference for female partners remained intact but androphilia was increased (e.g., Swift-Gallant et al., 2016b). One possibility is that there are species differences given that the first set of experiments reported were conducted in rats whereas the latter were in mice. Alternatively, these inconsistencies could be related to androgen dose timing: in the first set of studies supraphysiological levels of androgen were administered only during early critical periods whereas the latter studies, using transgenic mouse models, AR signaling was increased throughout the entire lifespan of the mouse. Future studies will be required to delineate the nature of these differences.
Ein 3-4 mal so hoher Stand an Testosteron wäre natürlich schon eine sehr deutliche Erhöhung. Was nicht bedeutet, dass sie nicht eintreten kann. Es wäre natürlich interessant wie das auf den Menschen zu übertragen ist, bei dem leider solche direkten Forschungen ja nun einmal nicht erfolgen können. Dazu aus den Schlussfolgerungen:
The field of behavioral neuroendocrinology has established principles of sexual differentiation dating back to the 1950’s that continue to guide research: androgens act during developmental critical periods to shape the brain and behavior. However, as the field progresses, we are unveiling complexities in the processes by which the brain undergoes sexual differentiation to lead to a myriad, rather than just the two long recognized sexual phenotypes. There is still a lot to learn about how sexual differentiation of the brain and behavior is affected by the interaction of androgenic and estrogenic pathways, site of hormone action, dose effects and environmental factors, among others. Fortunately, the field is sufficiently well established that we can begin to test whether the principles emerging from the rodent literature generalize to other species, including humans. There are sure to be differences in the details of how hormones affect the brain and behavior between species but given the many similarities in our biology, it is likely that the overarching themes will translate. Indeed, recent findings reviewed here support the hypothesis that there are multiple biological pathways that lead to same-sex sexual orientation, including both low and high androgen signaling in humans, as it does in mice. Although this review largely focused on the effects of prenatal androgens on androphilia in males, these principles likely also hold true for female sexual orientation. For example, the literature has consistently linked increased androgens to same-sex sexual attraction in women, but multiple factors are likely at play, given that biomarkers of androgen exposure and circulating testosterone are higher among more gender nonconforming (e.g., self-identified “butch”) compared to gender conforming lesbians (e.g., self-identified “femmes”; reviewed in Breedlove, 2017; Singh et al., 1999). Thus, it is likely that for both men and women, there exist more than a single bio-developmental pathway to same-sex sexual orientation. Further exploring such questions into the sexual differentiation of rodents and humans will contribute to our understanding of how individual differences develop in the brain and behavior.
Gerade weil Menschen und Mäuse beide Säugetiere sind und insofern starke Verwandtschaften haben, wird sich sicherlich einiges übertragen lassen. Vielleicht wären Forschungen an Affen da ganz interessant, wenn auch wesentlich aufwändiger.
Mal sehen, was die Forschung da noch alles rausfindet.
Während die Gender Studies noch fest darauf beharren, dass alles sozial begründet ist (bis auf vielleicht bei Transpersonen etc bei denen es dann doch wieder fest ist, aber warum das lässt man eher im Dunklen) zeigt die tatsächliche Wissenschaft schon die verschiedenen Wege auf, die jeweils das Ergebnis herbeiführen.