Brain sexual differentiation and gonadotropins secretion in the rat
Brain sexual differentiation and gonadotropins secretion in the rat
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DOI：
10.1023/a:1022542221535
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发表时间：
1997-12-01
影响因子：
4
通讯作者：
Libertun, C
中科院分区：
文献类型：
--
作者：
Becú-Villalobos, D;Iglesias, AG;Libertun, C
1.本工作涉及大鼠促性腺激素调节的性别差异以及下丘脑性组织在确定这种差异中的作用。雄性和雌性大鼠之间的性别差异，就它们对促性腺激素分泌的控制而言，不仅仅是促性腺激素是否周期性释放。大鼠表现出额外的性别差异(A)促性腺激素对去除和施加负反馈信号的反应，以及(B)从出生到青春期促性腺激素的个体发育。有一个敏感的发育期，在性腺激素的影响下，神经基质的性别分化不可逆转地进行。在大鼠中，这一时期从出生前几天开始，到出生后大约10天结束。雌性大鼠在这一敏感时期接受雄激素或雌激素治疗后，将永久丧失释放GnRH的能力，以回应雌激素刺激。然而，尽管性别分化受到新生儿期事件的极大影响，但最近的数据质疑这一时期的“关键”性质，因为已经表明，睾酮在新生儿期(15至30天)之后仍可作用于神经基质，使内分泌和行为功能去女性化和男性化。此外，女性性行为的正常表现和促性腺激素的循环释放的能力并不是中枢神经组织所固有的，而是依赖于发育敏感时期活跃的激素雌激素诱导。此外，在男性性脑功能分化过程中，雌激素对雄激素的主要作用可能是支持性的，而不是指导性的。5-羟色胺能系统、去甲肾上腺素能系统和阿片系统参与成年大鼠促性腺激素控制的性二型性。去势后黄体生成素升高的性别差异取决于下丘脑的早期性组织，即使在成年期也会受到多种因素的影响，如发情周期的阶段，动物的年龄，雌二醇的预处理，以及从反馈抑制中释放的历史。雌性幼年大鼠促性腺激素分泌的特征模式是性别分化的，这可能与垂体受体的增加与细胞内钙对GnRH的反应增加有关。这类事件取决于下丘脑性组织。在雄性动物中，30天后对GnRH的敏感性增加反映在垂体GnRH受体的增加上，而不是GnRH引起的钙动员幅度的增加，因此，在这种情况下，可能是替代的第二信使调节高敏感性。在婴儿期，新生儿下丘脑的雄激素化可能通过改变受体浓度和信号转导来降低脑垂体对促性腺激素释放激素的反应。最后，促性腺激素释放激素的5-羟色胺能、多巴胺能、阿片能和去甲肾上腺素能调节随着年龄的增长而变化，而睾酮或雌激素对下丘脑性组织的调节是这种调节的决定因素。
1. The present work deals with sexual differences in gonadotropin regulation in the rat and the role of sexual organization of the hypothalamus in determining such differences.2. Sex differences between male and female rats, with regard to their control of gonadotropin secretion, go beyond whether or not gonadotropins are released cyclically. Rats show additional sex differences (a) in the response of gonadotropins to removal and imposition of negative feedback signals and (b) in the ontogeny of gonadotropin regulation from birth to puberty.3. There is a sensitive developmental period during which sexual differentiation of neural substrates proceeds irreversibly under the influence of gonadal hormones. In the rat this period starts a few days before birth and ends approximately 10 days after birth. Female rats treated during this sensitive period with androgens or estrogens will permanently lose the capacity to release GnRH in response to estrogenic stimulation.4. Nevertheless although sexual differentiation is dramatically affected by events during the neonatal period, recent data question the "critical" nature of this period, as it has been shown that testosterone can still act on neural substrates well beyond (15 to 30 days of age) the neonatal period to defeminize and masculinize endocrine and behavioral functions.5. Furthermore, the capacity for the normal display of female sexual behavior and for the cyclic release of gonadotropins is not, as has been assumed, inherent to central nervous tissue but depends on active hormonal estrogenic induction during a sensitive period of development.6. Besides, during differentiation of male sexual brain function estrogens may be supportive, rather than directive, to the primary action of androgens.7. Serotonergic, noradrenergic, and opioid systems participate in the sexual dimorphism in gonadotropin control in adult rats.8. The sex difference in the postcastration LH rise is dependent on the early sexual organization of the hypothalamus, even though in adulthood it can also be influenced by a variety of factors such as the stage of the estrous cycle, age of the animal, estradiol pretreatment, and history of release from feedback inhibition.9. The characteristic pattern of gonadotropin secretion in the female infantile rat, which is sexually differentiatied, can be related to an increase in hypophyseal receptors coupled to an increase in the intracellular calcium response to GnRH. Such events depend on the sexual organization of the hypothalamus. In males the greater sensitivity to GnRH at 30 days is reflected in an increase in pituitary GnRH receptors but not in an increase in the magnitude of Ca2+ mobilization induced by GnRH, therefore it is probable that in this situation alternative second messengers may modulate high sensitivity. Neonatal androgenization of the hypothalamus may decrease the hypophyseal response to GnRH by an alteration in receptor concentration and signal transduction during the infantile period.10. Finally, serotonergic, dopaminergic, opioid, and noradrenergic regulation of GnRH varies with increasing age, and the sexual organization of the hypothalamus by testosterone or estrogens is a determinant in such regulation.