Sex Differences in the Distribution and Abundance of Androgen Receptor mRNA‐Containing Cells in the Preoptic Area and Hypothalamus of the Ram and Ewe

Scott, Christopher J.; Clarke, I. J.; Rao, Arathi; Tilbrook, Alan John

doi:10.1111/j.1365-2826.2005.01261.x

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…Similar findings have been reported in rats [60,61]. By contrast, sex differences in AR immunoreactivity favor males, with increased levels of AR mRNA and protein in MPOA and BST of male sheep [62], hamsters [63], rats [64], and mice [65]. Similar sex differences in AR were not identified in human brain [66].…”

Section: Estrogen Receptors In Fetal Lambs 1155supporting

confidence: 64%

Estrogen Receptor Immunoreactivity in Late-Gestation Fetal Lambs1

Gorton¹,

Mahoney²,

Magorien³

et al. 2009

Biology of Reproduction

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Prenatal androgens masculinize postnatal reproductive neuroendocrine function and behavior in sheep. Testosterone treatment of pregnant ewes during midgestation masculinizes sexual behavior and luteinizing hormone secretion in female lambs, presumably in part via aromatization and estrogen receptor (ESR) binding in the brain. We hypothesized that male and female sheep also differ in the number and distribution of ESR-containing neurons. If so, ESR expression should be sensitive to prenatal hormones delivered exogenously or in situ. ESR alpha (ESR1) was compared by immunocytochemistry in male and female lambs at the end of gestation, as well as in fetal females exposed prenatally to testosterone or dihydrotestosterone. ESR1-positive neurons were abundant in the posteromedial bed nucleus of the stria terminalis (BSTpm), medial preoptic area (MPOA), posterior medial amygdaloid nucleus (MeP), amygdalohippocampal area (AHi), ventromedial hypothalamic nuclei (VMH), and arcuate hypothalamic nuclei (ARC). In females, the ARC had the largest number of stained cells (mean 6 SEM, 475.6 6 57.4 cells/0.173 mm 2 ), while staining intensity was greatest in the MPOA (mean 6 SEM gray level, 31.3 6 5.3). The mean 6 SEM integrated gray level (IGL) was high in the ARC (0.63 6 0.13) and in the MPOA (0.51 6 0.08). The mean 6 SEM IGL was low in the MeP (0.31 6 0.10) and in the BSTpm (0.21 6 0.06), while it was intermediate in the AHi (0.36 6 0.10) and in the VMH (0.37 6 0.07). ESR immunostaining was not significantly different in male and female fetal lambs, nor in females fetuses exposed prenatally to androgens (P . 0.05). However, ESR1 staining was significantly increased in the ARC, MPOA, and AHi of adult rams vs. adult ewes. These results suggest that brain ESR immunoreactivity in fetal lambs is unlikely to account for postnatal sex differences in reproductive function. Instead, sex differences in ESR emerge postnatally.

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Section: Estrogen Receptors In Fetal Lambs 1155supporting

confidence: 64%

Estrogen Receptor Immunoreactivity in Late-Gestation Fetal Lambs1

Gorton¹,

Mahoney²,

Magorien³

et al. 2009

Biology of Reproduction

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“…This observation implies a unique role for the teleost esr1 in neural masculinization or defeminization. In addition, ara and arb are expressed at approximately equal levels between the sexes and at higher levels in females, respectively, in the medaka brain; this is in contrast to the situation in mammals, where Ar is generally expressed to a greater extent in the male brain than in the female brain, thus playing a critical role in the masculinization of reproductive behaviour [26][27][28][29]. These results suggest that androgen/ AR signalling has some relevance to feminization or demasculinization of the female brain in teleosts.…”

Section: Discussionmentioning

confidence: 86%

Female-specific target sites for both oestrogen and androgen in the teleost brain

et al. 2012

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To dissect the molecular and cellular basis of sexual differentiation of the teleost brain, which maintains marked sexual plasticity throughout life, we examined sex differences in neural expression of all subtypes of nuclear oestrogen and androgen receptors (ER and AR) in medaka. All receptors were differentially expressed between the sexes in specific nuclei in the forebrain. The most pronounced sex differences were found in several nuclei in the ventral telencephalic and preoptic areas, where ER and AR expression were prominent in females but almost completely absent in males, indicating that these nuclei represent female-specific target sites for both oestrogen and androgen in the brain. Subsequent analyses revealed that the female-specific expression of ER and AR is not under the direct control of sex-linked genes but is instead regulated positively by oestrogen and negatively by androgen in a transient and reversible manner. Taken together, the present study demonstrates that sex-specific target sites for both oestrogen and androgen occur in the brain as a result of the activational effects of gonadal steroids. The consequent sex-specific but reversible steroid sensitivity of the adult brain probably contributes substantially to the process of sexual differentiation and the persistent sexual plasticity of the teleost brain.

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“…Our present findings in PA females emulate this LH differential: Specifically, fetal PA females, when exposed to testosterone levels typical of those seen in the lower range of normal fetal males, have low circulating bio-LH levels compared with normal female controls at 80 days of gestation (second trimester). In fetal males and PA females alike, such LH suppression may represent testosterone-mediated changes in hypothalamic regulation of LH secretion [62], altered either directly via androgen receptors [63,64] or indirectly via estrogen receptors, through target tissue aromatization of exogenous testosterone [65,66].…”

Section: Discussionmentioning

confidence: 99%

Endocrine Antecedents of Polycystic Ovary Syndrome in Fetal and Infant Prenatally Androgenized Female Rhesus Monkeys1

Abbott

Barnett

Levine

et al. 2008

Biology of Reproduction

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Experimentally induced fetal androgen excess induces polycystic ovary syndrome-like traits in adult female rhesus monkeys (Macaca mulatta). Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily s.c. injections of 15 mg of testosterone propionate (TP), and six received injections of oil vehicle (control) from 40 through 80 days of gestation (term, 165 days; range, +/-10 days). All fetuses were delivered by cesarean section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. The TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels returned to values within the reference range for animals in these age groups, whereas serum androstenedione levels in PA infants were elevated. The TP injections did not increase estrogen levels in the dams or the PA fetuses or infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late-gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood.

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Sex Differences in the Distribution and Abundance of Androgen Receptor mRNA‐Containing Cells in the Preoptic Area and Hypothalamus of the Ram and Ewe

Cited by 27 publications

References 38 publications

Estrogen Receptor Immunoreactivity in Late-Gestation Fetal Lambs1

Estrogen Receptor Immunoreactivity in Late-Gestation Fetal Lambs1

Female-specific target sites for both oestrogen and androgen in the teleost brain

Endocrine Antecedents of Polycystic Ovary Syndrome in Fetal and Infant Prenatally Androgenized Female Rhesus Monkeys1

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