Independent masculinization of neuroendocrine systems by intracerebral implants of testosterone or estradiol in the neonatal female rat

Christensen, L. W.; Gorski, Roger A.

doi:10.1016/0006-8993(78)90977-0

Cited by 145 publications

(42 citation statements)

References 34 publications

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“…For example, this steroid is critical in development of the male brain, and masculinizes adult sexual behaviors (Amateau and McCarthy, 2004;Konkle and McCarthy, 2011; but see Adkins, 1979). In fact, estradiol is as effective as testosterone in masculinizing the regulation of gonadotropic hormone release in rats (Christensen and Gorski, 1978). Elevated levels of 14 estradiol also facilitate prostate development in fetal mice (vomSaal et al, 1997), but this pattern reverses when even higher doses are used.…”

Section: Discussionmentioning

confidence: 99%

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination

Warner¹,

Addis²,

Du³

et al. 2014

General and Comparative Endocrinology

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Steroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced male offspring across all incubation temperatures. These unexpected results were remarkably consistent across all four experiments and both study species. Elevated concentrations of estradiol could interact with androgen receptors or inhibit aromatase expression, which might result in relatively high testosterone concentrations that lead to testis development. These findings add to a short list of studies that report paradoxical effects of steroid hormones, which addresses the need for a more comprehensive understanding of the role of sex steroids in sexual development. KeywordsAromatase inhibitor, Chelydra serpentina, Chrysemys picta, Environmental sex determination, Sex steroids, Sexual differentiation Disciplines Aquaculture and Fisheries | Ecology and Evolutionary Biology | Other Ecology and Evolutionary Biology | Population Biology | ZoologyComments NOTICE: this is the author's version of a work that was accepted for publication in General and Comparative Endocrinology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in General and Comparative Endocrinology, 206 (2014) ABSTRACTSteroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced ...

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Section: Discussionmentioning

confidence: 99%

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination

Warner¹,

Addis²,

Du³

et al. 2014

General and Comparative Endocrinology

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“…Unlike the transient activational effects of steroids in adulthood, exposure to these steroids during a critical period in early development produces permanent, organizational changes in central nervous system structure and function (see Gorski, 1985). The size of the sexually dimorphic nucleus of the preoptic area in rats described by Gorski et al (1978) is perhaps the best-known example of organizational changes in the central nervous system (CNS). Functional changes associated with organizational effects of gonadal steroids include masculinization of sexual behaviour and defeminization of the LH surge (MacLusky and Naftolin, 1981).…”

Section: Masculinization Of the Brainmentioning

confidence: 99%

“…Functional changes associated with organizational effects of gonadal steroids include masculinization of sexual behaviour and defeminization of the LH surge (MacLusky and Naftolin, 1981). Within the broad critical period for sexual differentiation, each sexually dimorphic trait is presumed to have an individual period of susceptibility to steroids (that is, individual critical periods) (Clarke et al, 1976;Christensen and Gorski, 1978;Gorski and Jacobson, 1981). These critical periods occur prenatally in sheep and other species with long gestation periods (for example, primates and guinea-pigs); in contrast, the brain becomes sexually differentiated mostly in the first few days after birth in rats and other species with short gestation periods (Goy and McEwen, 1980).…”

Section: Masculinization Of the Brainmentioning

confidence: 99%

Sexual differentiation of reproductive neuroendocrine function in sheep

Wood

Foster²

1998

Reviews of Reproduction

116

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Puberty, the transition from a sexually immature state to one of full reproductive activity, is timed by signals acting in the brain to increase activity of the hypothalamo-pituitary axis which stimulates the production of mature gametes. There are profound sex differences in the timing of puberty in many species. This occurs by sexual differentiation of the neuroendocrine control of pituitary gonadotrophin secretion. Studies using sheep as an experimental model have defined some of the factors responsible for this developmental difference in reproductive neuroendocrine function. We have studied the prenatal organizers (prenatal steroids), postnatal cues (growth and photoperiod responses) and the effectors (GnRH neurones) that time the pubertal process. Our experimental strategy has been to conduct complementary anatomical and physiological investigations to link form and function in the sexual differentiation of reproductive neuroendocrine function. Reproductive strategies in males and femalesTo ensure that sexual activity will ultimately be successful, males and females respond to cues from both their internal and external environments. Mating is timed so that young are born when somatic conditions are appropriate and seasonal conditions are favourable. However, the differences in reproductive strategies between males and females can often be as wide as those between different species (Bronson, 1989). These differences arise because the time course of gametogenesis and the metabolic investments in reproduction can be quite different in the two sexes.The typical female mammal gives birth to relatively few offspring during her lifespan, but expends considerable energy in their growth and early development (for review, see Bronson, 1989). Thus, most of her reproductive effort is invested after mating. The metabolic demands of pregnancy and lactation are considerable, and can compromise the chances of survival of the female if begun at an inappropriate time. However, the gametic cycle of females is relatively short, and only a few days are required to develop a preovulatory follicle. Together, these factors encourage the immature female to delay sexual maturation until conditions are optimal. After puberty, the typical adult female living in natural conditions may have only a few fertile cycles in 1 year. For much of the year, she is reproductively suppressed as a result of pregnancy and lactation, seasonal anovulation or, possibly, inadequate food intake. Nonetheless, once internal and external cues are favourable, reproductive activity can be initiated rapidly.The male uses an entirely different strategy to time sexual activity. The typical polygynous male produces large numbers of offspring, but does little to ensure their survival. Thus, most of the energy for his reproductive effort is expended before mating, primarily in competition for females (Bronson, 1985). Even though the energetic demands for production of spermatozoa and seminal fluid are comparatively small, spermatogenesis takes weeks to months to c...

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“…Coordinates used for MPN microimplants were 0.29 mm rostral to bregma, 0.8 mm lateral to the midline, and 7.0 mm ventral from the pia. Testosterone and hydroxyflutamide were dissolved in a heated suspension of beeswax (VWR International) to a final concentration of 0.3 M (Christensen and Gorski, 1978;Lund et al, 2006), packed to a height of ϳ400 m, and ejected using a 28 gauge wire that extended 0.5 mm beyond the tip of the cannula. Experimental control animals received stereotaxically guided, unilateral implants of beeswax alone.…”

Section: Methodsmentioning

confidence: 99%

The Medial Preoptic Nucleus Integrates the Central Influences of Testosterone on the Paraventricular Nucleus of the Hypothalamus and Its Extended Circuitries

Williamson¹,

Bingham²,

Gray³

et al. 2010

J. Neurosci.

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Testosterone contributes to sex differences in hypothalamic-pituitary-adrenal (HPA) function in humans and rodents, but the central organization of this regulation remains unclear. The medial preoptic nucleus (MPN) stands out as an important candidate in this regard because it contains androgen receptors and projects to forebrain nuclei integrating cognitive-affective information and regulating HPA responses to homeostatic threat. These include the HPA effector neurons of the paraventricular nucleus (PVN) of the hypothalamus, medial amygdala, and lateral septum. To test the extent to which androgen receptors in the MPN engage these cell groups, we compared in adult male rats the effects of unilateral microimplants of testosterone and the androgen receptor antagonist hydroxyflutamide into the MPN on acute restraint induced activation and/or neuropeptide expression levels. The basic effects of these implants were lateralized to the sides of the nuclei ipsilateral to the implants. Testosterone, but not hydroxyflutamide implants, decreased stress-induced Fos and arginine vasopressin (AVP) heteronuclear RNA expression in the PVN, as well as Fos expression in the lateral septum. In unstressed animals, AVP mRNA expression in the PVN decreased and increased in response to testosterone and hydroxflutamide MPN implants, respectively. The differential influences of these implants on AVP mRNA expression were opposite in the medial amygdala. These results confirm a role for androgen receptors in the MPN to concurrently modulate neuropeptide expression and activational responses in the PVN and its extended circuitries. This suggests that the MPN is capable of bridging converging limbic influences to the HPA axis with changes in gonadal status.

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Independent masculinization of neuroendocrine systems by intracerebral implants of testosterone or estradiol in the neonatal female rat

Cited by 145 publications

References 34 publications

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination

Sexual differentiation of reproductive neuroendocrine function in sheep

The Medial Preoptic Nucleus Integrates the Central Influences of Testosterone on the Paraventricular Nucleus of the Hypothalamus and Its Extended Circuitries

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