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Biomedical subjects

S Marc Breedlove

Publications and source records attributed to S Marc Breedlove.

At least 19 recordsLinked to original sources
PubMed2006

Androgen-sensitivity of somata and dendrites of spinal nucleus of the bulbocavernosus (SNB) motoneurons in male C57BL6J mice.

In rats, androgens in adulthood regulate the morphology of motoneurons in the spinal nucleus of the bulbocavernosus (SNB), including the size of their somata and the length of their dendrites. There are conflicting reports about whether androgens exert similar influences on SNB motoneurons in mice. We castrated or sham-operated C57BL6J mice at 90 days of age and, thirty days later, injected cholera toxin conjugated horseradish peroxidase into the bulbocavernosus muscle (to label SNB motoneurons) on one side, and into intrinsic foot muscles contralaterally (to label motoneurons of the retrodorsolateral nucleus (RDLN)). Castrated mice had significantly smaller SNB somas compared to sham-operated mice while there were no differences in soma size of RDLN motoneurons. Dendritic length in C57BL6J mice, estimated in 3-dimensions, also decreased significantly after adult castration. In rats, androgens act directly through androgen receptors (AR) in SNB motoneurons to control soma size and nearly all SNB motoneurons contain AR. Since SNB somata in C57BL6J mice shrank after adult castration, we used immunocytochemistry to characterize AR expression in SNB cells as well as motoneurons in the RDLN and dorsolateral nucleus (DLN). A pattern of labeling matched that seen previously in rats: the highest percentage of AR-immunoreactive motoneurons are in the SNB (98%), the lowest in the RDLN (25%) and an intermediate number in the DLN (78%). This pattern of AR labeling is consistent with the possibility that androgens also act directly on SNB motoneurons in mice to regulate soma size in mice.

Analysis of Variance↗
PubMed2006

Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats.

The ventromedial hypothalamus (VMH) is one of several sexually dimorphic nuclei that regulate mating behavior, and is rich in steroid hormone receptors and aromatase activity. We looked at the contribution of the androgen receptor (AR) to the volume of the VMH in rats by measuring each of the four subdivisions of the VMH in 90 day old male, female, and XY male rats carrying a mutant AR allele (tfm), which renders animals largely unresponsive to androgens. Confirming published reports, total VMH volume was greater in wild-type males than in females (P<0.01). The mean total volume of the VMH in TFM males was intermediate, but not significantly different from either females or males (Ps>0.10). The sex difference in VMH volume was primarily accounted for by the ventrolateral subdivision (VMHvl), which in both females and TFM males was significantly smaller than in wild-type males (Ps<0.005). There was no significant sex difference in the volume of the other three subdivisions of the VMH. Neuronal somata were larger in males than females in VMHvl, central VMH (VMHc) and the dorsomedial VMH (VMHdm), with TFM males having feminine neuronal somata in the VMHdm and VMHc. These data suggest that AR plays a role during sexual differentiation of the VMH, imparting its greatest effect in the VMHvl. ARs may regulate aromatase expression or activity to affect estrogen receptor activation, or may act independently of estrogen receptors to influence VMH morphology.

Analysis of Variance↗
PubMed2006

Sex differences in digit ratio (2D:4D) are disrupted in adolescents with schizotypal personality disorder: altered prenatal gonadal hormone levels as a risk factor.

The 2nd to 4th finger digit ratio (2D:4D) is a sexually dimorphic feature determined during gestation indexing prenatal androgen/estrogen levels. More 'feminized' 2D:4D phenotype has been demonstrated in schizophrenia versus same-sex controls. This study examined 2D:4D in adolescents with schizotypal personality disorder (SPD). Among normal controls, right 2D:4D was significantly greater (more feminized) in females than males. We replicated laterality effects; significant sex differences only on right. There were no significant sex differences among SPDs. Diagnostic group differences were restricted to White/Caucasian males with greater right 2D:4D in SPDs. Findings suggest disruptions in prenatal gonadal hormones in vulnerability for schizophrenia.

Adolescent↗
PubMed2006

Anabolic responsiveness of skeletal muscles correlates with androgen receptor protein but not mRNA.

Anabolic effects of androgens on skeletal muscle are well documented, but the physiological and biochemical bases of these effects are poorly understood. Skeletal muscles that differ in their androgen responsiveness can be used to examine these mechanisms. We compared androgen receptor mRNA and protein levels of the rat levator ani, a perineal skeletal muscle that depends on androgens for its normal maintenance and function with that of the rat extensor digitorum longus, a limb muscle that does not require androgens. Western immunoblotting indicated that androgen receptor protein is significantly elevated in the levator ani relative to the extensor digitorum longus. Surprisingly, steady state androgen receptor mRNA levels were equivalent in these muscles, as determined by Northern blot analysis and quantitative RT-PCR. These results suggest that androgen responsiveness of skeletal muscles is determined by the level of androgen receptor protein in a particular muscle and that androgen receptor protein content is regulated by translational or post-translational mechanisms.

Anabolic Agents↗
PubMed2005

Preliminary evidence that gonadal hormones organize and activate disordered eating.

OBJECTIVE: Eating disorders are more common in females than in males. Gender differences may be due to organizational (i.e. prenatal) and activational (i.e. post-natal) gonadal hormone effects that influence sex differences in behavior. This preliminary set of studies examined these effects by investigating relationships between eating disorder symptoms, prenatal testosterone exposure, and adult levels of estrogen in women. METHOD: We examined organizational associations by investigating relationships between disordered eating and finger-length ratios, which are known to be somatic markers of prenatal testosterone exposure. Participants included 113 adult female twins drawn from the community. Disordered eating was assessed with the total score from the Minnesota Eating Behavior Survey (MEBS). Finger lengths were hand scored using a ruler and photocopies of both hands. We also investigated activational influences by examining associations between circulating levels of estradiol and disordered eating symptoms. Two independent samples of adult females (n's = 24 and 25) drawn from the community were used for this study. Disordered eating was again assessed with the MEBS total score, while saliva samples were used for assessing estradiol. RESULTS: Positive associations were found between disordered eating and both finger-length ratios and circulating estradiol levels. CONCLUSIONS: Findings suggest that lower levels of prenatal testosterone exposure and higher adult levels of estradiol are associated with increased eating disorder symptoms. We hypothesize that the relatively low level of testosterone before birth in females permits their brains to respond to estrogens at puberty, when the hormones activate the genes contributing to disordered eating in vulnerable girls.

Adolescent↗
PubMed2005

Interaction of fraternal birth order and handedness in the development of male homosexuality.

The present study investigated evidence for an interaction between two of the best established etiologic factors, or markers of etiologic factors, in the literature on male homosexuality: fraternal birth order and hand preference. By combining five samples, the authors produced study groups of 1774 right-handed heterosexuals, 287 non-right-handed heterosexuals, 928 right-handed homosexuals, and 157 non-right-handed homosexuals. The results showed a significant (P = 0.004) handedness by older brothers interaction, such that (a) the typical positive correlation between homosexuality and greater numbers of older brothers holds only for right-handed males, (b) among men with no older brothers, homosexuals are more likely to be non-right-handed than heterosexuals; among men with one or more older brothers, homosexuals are less likely to be non-right-handed than heterosexuals, and (c) the odds of homosexuality are higher for men who have a non-right hand preference or who have older brothers, relative to men with neither of these features, but the odds for men with both features are similar to the odds for men with neither. These findings have at least two possible explanations: (a) the etiologic factors associated with non-right-handedness and older brothers-hypothesized to be hyperandrogenization and anti-male antibodies, respectively-counteract each other, yielding the functional equivalent of typical masculinization, and (b) the number of non-right-handed homosexuals with older brothers is smaller than expected because the combination of the older brothers factor with the non-right-handedness factor is toxic enough to lower the probability that the affected fetus will survive.

Birth Order↗
PubMed2005

Partial demasculinization of several brain regions in adult male (XY) rats with a dysfunctional androgen receptor gene.

The adult rat posterodorsal medial amygdala (MePD) is sexually dimorphic in regional volume and neuronal soma size, both of which are larger in males than in females. This sexual dimorphism is entirely dependent on adult circulating levels of testicular androgens, and both androgen and estrogen treatment can masculinize MePD structure. We examined male rats that are rendered androgen-insensitive by the testicular feminization mutation (tfm) of the androgen receptor (AR) gene to determine how a dysfunctional AR affects this and other brain sexual dimorphisms. In adult wild-type rats, the MePD in males had a greater regional volume, rostrocaudal extent, and soma size than in females. In genetic males, defective ARs affected some but not all of these indices: MePD volume and soma size in tfm males were intermediate between those of wild-type males and females, but the rostrocaudal extent of the MePD was unaffected by the mutation, being as great in tfm males as in wild-type males. Regional volume and soma size in the suprachiasmatic nucleus was reduced in tfm males compared with wild-type males, suggesting that AR normally affects this region in male rats. Interestingly, whereas volume of the sexually dimorphic nucleus of the preoptic area was unaffected by the tfm allele, soma size in this region was reduced in tfm males compared with wild-type males. Although estrogen receptor activation has been shown to be vital for masculinization of the rodent brain, our results indicate that ARs also contribute to this process in several brain regions.

Amygdala↗
PubMed2005

A reanalysis of five studies on sexual orientation and the relative length of the 2nd and 4th fingers (the 2D:4D ratio).

Five studies have examined the relationship between sexual orientation and the relative lengths of the 2nd and 4th fingers (the 2D:4D ratio). Although differences have commonly been found between heterosexuals and homosexuals, the direction of the difference has not been consistent across studies. The original data from all five studies were reanalyzed in a search for possible explanations of the discrepancies. Because ethnicity is known to affect the 2D:4D ratio, the reanalysis focused on participants who identified themselves as White or Caucasian, the ethnic group that was most numerous in all of the studies. Age differences did not account for the discrepancies. Differences in variability within different groups were minor. One interesting result to emerge from the reanalysis was that the 2D:4D ratios for the homosexual groups were relatively similar across studies. It was the 2D:4D values for the heterosexual participants that varied most, particularly between the USA and the British studies, and these were responsible for many of the discrepancies in the conclusions across studies. The constancy of the 2D:4D ratio for the White homosexuals did not appear to extend to homosexuals of three other ethnicities, and there were also subpopulation differences related to right or left hands.

Adult↗
PubMed2004

Steroid hormone masculinization of neural structure in rats: a tale of two nuclei.

We review the mechanisms by which steroid hormones masculinize two different regions of the central nervous system (CNS) in rats. Although in both cases, androgens induce a male phenotype, the detailed mechanisms are remarkably different in the two models. In the spinal nucleus of the bulbocavernosus (SNB), testosterone must be present during the perinatal period to spare motoneurons and their target muscles from cell death. This masculinization of the SNB system is through activation of androgen receptors, because XY rats with a defective gene for the androgen receptor fail to develop a masculine SNB system. Interestingly, the motoneurons are spared by androgen, even though they themselves do not possess androgen receptors during the critical period for their survival. Thus, steroids can act on one part of the body to secondarily masculinize the CNS. In the posterodorsal aspect of the medial amygdala (MePD), testosterone can induce masculine development even in adulthood, indicating that there is no critical period for steroids to affect sexual differentiation of this system. In the case of the MePD, both estrogen receptors and androgen receptors appear to mediate testosterone's masculinizing influence on neural structure. The extended neural plasticity of the MePD may reflect annual "reorganization" of the brain in the seasonally breeding ancestors of laboratory rats.

Amygdala↗
PubMed2004

Sexual differentiation of the vertebrate nervous system.

Understanding the mechanisms that give rise to sex differences in the behavior of nonhuman animals may contribute to the understanding of sex differences in humans. In vertebrate model systems, a single factor-the steroid hormone testosterone-accounts for most, and perhaps all, of the known sex differences in neural structure and behavior. Here we review some of the events triggered by testosterone that masculinize the developing and adult nervous system, promote male behaviors and suppress female behaviors. Testosterone often sculpts the developing nervous system by inhibiting or exacerbating cell death and/or by modulating the formation and elimination of synapses. Experience, too, can interact with testosterone to enhance or diminish its effects on the central nervous system. However, more work is needed to uncover the particular cells and specific genes on which testosterone acts to initiate these events.

Animals↗
PubMed2003

Both estrogen receptors and androgen receptors contribute to testosterone-induced changes in the morphology of the medial amygdala and sexual arousal in male rats.

In male rats, a steroid-sensitive circuit in the forebrain regulates mating behavior. The masculine phenotype in one component of the circuit, the posterodorsal nucleus of the medial amygdala (MePD), depends on the level of circulating androgens in the adult. To investigate which gonadal steroid receptor(s) mediate sexual arousal and MePD plasticity, adult male rats were castrated and given Silastic capsules containing the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol (E2), both steroids, or nothing. A fifth group was sham-castrated and treated with blank capsules. DHT treatment was necessary and sufficient to maintain the expression of noncontact penile erections and ultrasonic vocalizations in castrates. E2 had no significant effect on these measures. Both DHT and E2 increased olfactory investigation ("nosepokes") during the noncontact penile erection test. E2, but not DHT, maintained intromission patterns, while either steroid, alone or in combination, maintained ejaculatory behavior. Regional volume and cell soma size of the MePD both decreased following castration. Additionally, MePD cell size was lateralized, with left hemisphere neurons larger than those on the right, an effect that appeared independent of steroid manipulations. DHT and E2 each maintained neuronal soma size. E2 maintained MePD regional volume more effectively in the left MePD than in the right, which may have been due to a greater sensitivity of the left to both castration and hormone treatment. Thus, both androgen receptors and estrogen receptors appear to participate in sexual behaviors that may be mediated by the MePD in adult rats, and both receptors contribute to the steroid-regulated structural plasticity in this brain region.

Amygdala↗
PubMed2002

Evidence that androgen acts through NMDA receptors to affect motoneurons in the rat spinal nucleus of the bulbocavernosus.

In adult male rats, spinal nucleus of the bulbocavernosus (SNB) motoneurons shrink after castration and are restored in size after androgen treatment. Sixty-day-old Sprague Dawley males were castrated and implanted with SILASTIC capsules containing testosterone (T) or nothing, and osmotic minipumps continuously infusing MK-801, a noncompetitive NMDA receptor antagonist, or saline. Twenty-five days later, bulbocavernosus muscles were injected with the retrograde tracer cholera toxin-horseradish peroxidase conjugate (CT-HRP) to label SNB cells. As seen previously, among saline-treated rats, SNB somata of T-treated castrates were significantly larger than those of castrates receiving blank capsules (p < 0.0001). MK-801 treatment blocked this effect of T on the SNB. MK-801 had no effect on non-androgen-responsive spinal motoneurons in the neighboring retrodorsolateral nucleus (RDLN), nor did the drug affect SNB soma size in the absence of androgen treatment. Motoneuronal soma size in Nissl stain revealed the same pattern of results seen with CT-HRP fills. In situ hybridization indicated that SNB motoneurons express mRNA for the NMDA receptor subunits R1, R2a, and R2b. Castration reduced the expression of R1 mRNA in SNB motoneurons, an effect that was blocked by androgen replacement in castrates. R2A and R2B mRNA expression in SNB cells was not affected by androgen manipulations. Likewise, androgen manipulations had no effect on the expression of any NMDA receptor subtypes in RDLN motoneurons. These results suggest that androgen affects the size of SNB motoneurons by influencing their expression of the NMDA receptor, and therefore the response of the motoneurons to endogenous glutamate.

Animals↗
PubMed2002

Sexual dimorphism in digit-length ratios of laboratory mice.

The lengths of the index finger (2D) and ring finger (4D) are sexually dimorphic in humans, and men have a smaller 2D:4D ratio compared to women. Prenatal androgens appear to be important in the development of the 2D:4D sex difference, since it has been reported in children as young as 2 years old, and since humans exposed to supernormal prenatal androgen levels display a smaller 2D:4D ratio. We tested whether another mammalian species in which the process of peripheral sexual differentiation is androgen-dependent might also show a sex difference in digit ratios. The 2D:4D ratio of adult outbred mice was calculated for both the left and right rear paws. A sex difference was observed in the right rear paw: female mice had a larger 2D:4D ratio than did males. We also found this difference in prepubescent weanling mice. This sex difference is in the same direction as that observed in humans, and suggests that sexual dimorphism in digit length ratios is a feature common to many, if not all, mammals. The mouse may therefore be a useful animal model for studying the factors that influence finger length patterns, which have recently been correlated with several specific behaviors and disease predispositions in humans.

Age Factors↗