Sex Difference in Whole-Body Androgen Content in Rats on Fetal Days 18 and 19 Without Evidence that Androgen Passes from Males to Females1

Baum, Michael J.; Woutersen, P. J. A.; Slob, A. Koos

doi:10.1095/biolreprod44.5.747

Cited by 90 publications

(50 citation statements)

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Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

“…Quantitative examination of androgens in fetal rats shows that males and females have similar androgen content during much of gestation (Baum et al 1991;Weisz and Ward 1980). However, concentrations of androgens in males increase significantly late in gestation (Baum et al 1991;Houtsmuller et al 1995;vom Saal and Bronson 1980;Weisz and Ward 1980), reaching a peak around the critical developmental window of GDs 18-19 (Baum et al 1991). Several studies have suggested that this brief exposure to elevated androgens late in gestation sensitizes the developing male to androgen exposure during the neonatal period (Baum et al 1990;Hoepfner and Ward 1988;Tobet and Baum 1987).…”

Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

“…Therefore, potential variation in prenatal testosterone may interact with or alter the sensitivity to endocrine-disrupting chemicals (EDCs). However, even during this critical window, developing female fetuses have significant testosterone concentrations in many different tissues, including those critical for the developing reproductive system (Baum et al 1991;Houtsmuller et al 1995;Weisz and Ward 1980). In several cases, individual female concentrations of testosterone are within the range experienced by males (Hotchkiss et al 2000;Weisz and Ward 1980).…”

Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

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Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

Hotchkiss

Ostby

VanDenburgh

et al. 2002

Environ Health Perspect

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In mammals, exposure to androgens early in development is essential for masculinization of the male reproductive phenotype. Male fetuses exposed to antiandrogens during perinatal life are permanently demasculinized in their morphology and physiology, whereas exposure to exogenous androgens permanently masculinizes females. In some litter-bearing species, proximity in utero of females to males can partially masculinize female siblings and alter their responsiveness to endocrine-disrupting compounds. However, in our strain of rat (CD-SD Charles River), intrauterine position does not significantly influence testosterone concentrations and anogenital distance of fetuses. In comparison, administration of testosterone propionate to pregnant females, at doses that doubled fetal female testosterone levels, did masculinize the reproductive system. Discovery of androgen-active chemicals in the environment has placed increased emphasis on describing the reproductive and behavioral effects of both natural and environmental androgens and antiandrogens. Recently, the effects of an antiandrogen, vinclozolin, on the brain and behavior were cited as a special concern by the U.S. Environmental Protection Agency in its risk assessment of this pesticide. In rats, one such behavior that is perinatally organized by androgens is social play. Males play more than females, and administration of exogenous androgens during the neonatal period alters the juvenile expression of this sexually dimorphic behavior. Vinclozolin is an androgen receptor antagonist that inhibits androgen-dependent tissue growth in vivo. We were interested in whether developmental exposure to vinclozolin could also alter androgen-dependent behaviors such as play. Neonatal male rats were injected on postnatal days (PNDs) 2 and 3 with corn oil, the pharmacologic antiandrogen flutamide (50 mg/kg), or vinclozolin (200 mg/kg). On PNDs 36-37 animals were observed for social play. Behaviors associated with general social activity such as sniffing and dorsal contact were unaffected by treatment. However, play behavior in males treated with flutamide or vinclozolin was significantly reduced, resembling levels of play characteristic of females rather than untreated males. Therefore, this study demonstrates that perinatal exposure to vinclozolin, an environmental antiandrogen, can alter androgen-dependent play behavior in the male rat.

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Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

Section: Natural Variation In Androgen Concentrations During Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

Hotchkiss

Ostby

VanDenburgh

et al. 2002

Environ Health Perspect

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“…Therefore, we cannot determine from the present data whether or not sexual differentiation of forebrain ARs occurs and, if it happens, whether it takes place pre-or neonatally under the influence of androgens or estrogens. 9,10,43,45,51,53 Future studies should address these questions.…”

Section: Androgen Receptor Immunoreactivitymentioning

confidence: 99%

Quantitative estimation of estrogen and androgen receptor-immunoreactive cells in the forebrain of neonatally estrogen-deprived male rats

et al. 1997

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Abstract--Using quantitative immunocytochemical procedures, the total number of estrogen and androgen receptors was estimated in a large number of hypothalamic and limbic nuclei of male rats, in which brain estrogen formation was inhibited neonatally by treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione. The highest densities of estrogen receptor immunoreactivity were observed in the periventricular preoptic area and the medial preoptic area. Neonatally estrogen-deprived males showed a higher estrogen receptor immunoreactivity than control males in the periventricular preoptic area and the ventrolateral portion of the ventromedial nucleus of the hypothalamus, i.e. those brain areas in which sex differences have been reported, with female rats showing a greater estrogen binding capacity than male rats. The highest densities of androgen receptor immunoreactivity were found in the septohypothalamic nucleus, the medial preoptic area, the posterior division of the bed nucleus of the stria terminalis and the posterodorsal division of the medial amygdaloid nucleus. No significant differences in distribution or total numbers of androgen receptors were found between neonatally estrogen-deprived males and control males.These findings suggest that neonatal estrogens, derived from the neural aromatization of testosterone, are involved in the sexual differentiation of the estrogen receptor system in the periventricular preoptic area and the ventromedial hypothalamus. The role of neonatal estrogens in the development of the forebrain androgen receptor system is less clear. 1997 IBRO. Published by Elsevier Science Ltd.Key words: neonatal ATD treatment, androgen receptor, estrogen receptor, estrogens, hypothalamus, preoptic area.In mammals, testosterone and estradiol derived from neural aromatization of testosterone act synergistically in the developing male brain to organize its structures and functions, i.e. to masculinize and defeminize the neural substrates that later control sexual behavior and neuroendocrine function. In the rat brain, masculinization results in the display of male-typical sexual behavior (mounts, intromissions and ejaculations) in adulthood. Defeminization results in a loss of cyclic release of gonadotropins necessary for ovulation and a loss of female-typical sexual behavior (lordosis, presenting, ear wiggling, hop and dart) in adulthood (e.g., Ref. 37). Thus, gonadally intact male rats display the complete pattern of male coital behavior when pair tested with an estrous female and no female-typical sexual behavior when pair tested with a sexually active male. However, lordosis behavior can be induced in castrated male rats by administering estradiol and progesterone, although the behavior displayed is usually less intense than that of females, and considerably more estradiol is required for its stimulation. 20,42,54 The development of the female rat brain is generally believed to proceed in the absence of testosterone and estradiol. Gonadally intact female rats display periods of be...

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“…Both testosterone and estradiol are necessary for normal sexual differentiation of the male brain [98]. In developing females, although it has been proposed that the fetal ovary is relatively quiescent compared to the male testis, it is important to note that androgens and estrogens are measurable in the late embryonic period in female rats [13,70]. However, sexual differentiation of the female and male brain still differs due in part to alpha-fetoprotein, which protects the brain from effects of maternal estrogens [10,42].…”

Section: Introduction To Development Of Reproductive Neuroendocrine Cmentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

231

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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Sex Difference in Whole-Body Androgen Content in Rats on Fetal Days 18 and 19 Without Evidence that Androgen Passes from Males to Females1

Cited by 90 publications

References 0 publications

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

Quantitative estimation of estrogen and androgen receptor-immunoreactive cells in the forebrain of neonatally estrogen-deprived male rats

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

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