SEX STEROID BINDING PROTEIN AND ANDROGEN ACTION

本研究将探讨植物生长因子的生理调节和作用， 性类固醇结合蛋白（SBP）在男性。 SBP是一种B球蛋白， 表现出高亲和力结合睾酮（T），主要的循环 雄激素 这种蛋白质的血浆水平已被证明会增加 在人、猴子、蝙蝠、兔子和仓鼠出生后明显， 在季节性繁殖者的繁殖更新中。 目前的概念 SBP可能在改变额外和 T细胞内分布、代谢和可用性。 因此，任何 SBP水平的增加预计会影响 循环雄激素 初步研究表明， 出生后和季节性收缩压活动的增加受到 甲状腺 为了研究该腺体在SBP调节中的作用， 将在Djungarian中测量总T3和游离T4的血浆水平 仓鼠，并与SBP水平的急剧增加相关， 在这个物种中出生后才发生。 平行研究将在 蝙蝠在实验室引起的季节性SBP上升。 此外该 SBP水平与L-T4和D-T4之间的剂量-反应关系如下： 在无甲状腺的男性中测定。 探讨SBP在雄激素调节中的作用 作用，将采用两种动物模型：1）去势雄性大鼠， 缺乏内源性SBP的动物，因此允许 通过控制慢性输注SBP和T进行操作;以及2） 雄性蝙蝠，一种内源性收缩压水平增加30倍的哺乳动物， 可以通过实验诱导。 利用大鼠模型， 前列腺、精囊和前列腺上的搏动性T信号 下丘脑/垂体对LH分泌的调节将在以下条件下确定： 高水平和低水平外源性SBP的条件下。 使用蝙蝠模型，R1881对靶组织的雄激素激活， 一种合成类固醇，与靶组织中的雄激素受体结合， 未达到SBP，将进行评价。 之间的剂量-反应关系 这种雄激素和目标反应将在高水平的蝙蝠中建立， 低收缩压水平。 这些体内研究的结果，加上 使用免疫细胞化学对SBP进行血管外定位， 关于SBP在雄激素靶点作用中的作用的有价值信息 组织水平。

This proposal will investigate the physiological regulation and actions of sex steroid-binding protein (SBP) in the male. SBP is a B-globulin that exhibits high-affinity binding of testosterone (T), the major circulating androgen. Plasma levels of this protein have been shown to increase markedly after birth in man, monkeys, bats, rabbits, and hamsters, and also during reproductive renewal in seasonal breeders. Current concepts hold that SBP may play an important role in altering the extra- and intracellular distribution, metabolism, and availability of T. Thus, any increases in SBP levels would be expected to influence the action of circulating androgens. Preliminary studies have suggested that both the postnatal and seasonal increases in SBP activity are influenced by the thyroid. To investigate the role of this gland in the regulation of SBP, plasma levels of total and free T3 and T4 will be measured in Djungarian hamsters and correlated with the dramatic increases in SBP levels which occur postnatally in this species. Parallel studies will be conducted in bats during the laboratory-induced seasonal SBP rise. In addition, the dose-response relationship between SBP levels and both L- and D-T4 will be determined in athyrotic males. To investigate the role of SBP in androgen action, two animal models will be employed: 1) the castrated male rat, an animal which lacks an endogenous SBP and thus allows the independent manipulation, by controlled chronic infusions, of both SBP and T; and 2) the male bat, a mammal in which a 30-fold increase in endogenous SBP levels can be induced experimentally. Using the rat model, the effectiveness of pulsative T signals on the prostate, the seminal vesicles, and the hypothalamic/pituitary regulation of LH secretion will be determined under conditions of both high and low levels of exogenously-administered SBP. Using the bat model, the androgenic activation of target tissues by R 1881, a synthetic steroid which binds to androgen receptors in target tissues but not to bat SBP, will be evaluated. Dose-response relationships between this androgen and target response will be established in bats with high and low SBP levels. The results from these in vivo studies, coupled with the extravascular localization of SBP using immunocytochemistry, will provide valuable information on the role of SBP in androgen action at the target tissue level.