Adenylyl cyclase activities in ovarian tissues. II. Regulation of responsiveness to LH, FSH, and PGE1 in the rabbit.
Adenylyl cyclase activities in ovarian tissues. II. Regulation of responsiveness to LH, FSH, and PGE1 in the rabbit.
复制标题
卵巢组织中的腺苷酸环化酶活性。
作者：
M. Hunzicker;L. Birnbaumer
我们进行了一项研究，以确定排卵前卵泡积累cAMP的能力是否下降，以响应体外黄体生成素暴露，Marsh等人报道。(1)是由于黄体生成素-人绒毛膜促性腺激素反应的腺酰环化酶(AC)系统直接脱敏所致。用交配(内源性促黄体生成素释放)或注射hCG(100IU/3.5-4.5g，iv)的方法，对分离的Graafian卵泡在排卵前和排卵后不同时间制备的匀浆中的酶活性进行了测定。这两种处理都导致AC对促黄体生成素和卵泡刺激素的刺激不敏感，因此到排卵时这些反应就消失了。HCG诱导的脱敏迅速(注射后5分钟内50%的促黄体生成素刺激活性丧失)，呈剂量依赖关系，需要排卵剂量；对促黄体生成素和卵泡刺激素刺激的活性具有选择性，对基础和前列腺素E_1以及氟化钠刺激的活性没有影响；被黄体生成素(交配)和hCG-FSH和催乳素特异性诱导，但不起作用。卵泡AC的脱敏似乎不是由PG介导的，因为抑制排卵的剂量的吲哚美辛并不干扰黄体生成素反应性的丧失。分离的Graafian(发情)卵泡与黄体生成素(2 H)孵育后，对黄体生成素的刺激也有脱敏作用，表明这一现象是由于黄体生成素对卵泡的直接作用所致，而不是由来自其他内分泌结构的激素介导的。新形成的黄体(CL)在妊娠或假孕(PSP)中形成了一种新的AC系统，该系统对黄体生成素高度敏感，对卵泡刺激素和前列腺素E_1反应较弱。这一新系统在妊娠和PSP期间持续存在，并随着CL的消退而变得不活跃。子宫切除术后PSP的延长伴随着活跃的促黄体生成素反应性AC系统的持续存在。给6天龄的PSP兔注射排卵量的hCG，在2小时内使黄体AC系统对促黄体生成素的刺激脱敏50%。妊娠10天后，由Challis等人报道的促黄体生成素刺激的CL中AC活性水平和血清孕酮水平。(2)，这一酶活性可能是孕酮合成的一个生理调节步骤，在动物妊娠的大部分时间里，正常的CL可能是一个生理调节步骤。这一发现是根据令人信服的证据来讨论的，即雌激素在兔子体内是促黄体的。
We conducted a study to determine whether a decline in the capacity of preovulatory follicles to accumulate cAMP in response to in vitro LH exposure, reported by Marsh et al. (1), is due to direct desensitization of the LH-hCG-responsive adenylyl cyclase (AC) system. Enzyme activity was determined in the absence and in the presence of 10 mug/ml of LH, FSH, and prostaglandin (PG) E1 in homogenates prepared from Graafian follicles dissected before and at various times after rendering them preovulatory either by mating (endogenous LH release) or by injection of hCG (100 IU/3.5-4.5 g rabbit, iv). Both of these treatments resulted in desensitization of the AC to LH and FSH stimulation, so that by the time of ovulation these responses were absent. hCG-induced desensitization was rapid (50% loss of LH-stimulated activity was obtained within 5 min of injection), was dose-dependent, requiring an ovulatory dose; was selective for LH- and FSH-stimulated activity, being without effect on basal and PGE1 as well as NaF-stimulated activities; and was induced specifically by LH (mating) and hCG-FSH and PRL being without effect. Desensitization of follicular AC does not seem to be mediated by PG, for doses of indomethacin that inhibited ovulation did not interfere with the loss of LH responsiveness. The incubation in vitro of dissected Graafian (estrous) follicles with LH (2 h) also resulted in desensitization to LH stimulation and indicated that this phenomenon was due to a direct effect of LH on the follicles and was not mediated by hormones derived from other endocrine structures. Newly formed corpora lutea (CL) in either pregnancy or pseudopregnancy (PSP) developed a new AC system that was highly responsive to LH and less responsive to FSH and PGE1. This new system persisted for the duration of pregnancy and PSP, and became inactive with regression of CL. The prolongation of PSP by hysterectomy was accompanied by the persistence of an active LH-responsive AC system. The injection of ovulatory doses of hCG into 6-day PSP rabbits produced, within 2 h, a 50% desensitization of the luteal AC systems to LH stimulation. After day 10 of pregnancy, the levels of LH-stimulated AC activity in CL and the levels of progesterone in serum, reported by Challis et al. (2), were found to parallel each other, suggesting that this enzyme activity may be a physiologic regulatory step in progesterone synthesis by the normal CL throughout most of the animal's pregnancy. This finding is discussed in the light of compelling evidence that estrogens are luteotrophic in the rabbit.