GONADOTROPIN-RELEASING-HORMONE (GNRH) RECEPTOR DYNAMICS AND GONADOTROPE RESPONSIVENESS DURING AND AFTER CONTINUOUS GNRH STIMULATION
GONADOTROPIN-RELEASING-HORMONE (GNRH) RECEPTOR DYNAMICS AND GONADOTROPE RESPONSIVENESS DURING AND AFTER CONTINUOUS GNRH STIMULATION
复制标题
DOI：
10.1095/biolreprod35.4.881
复制
发表时间：
1986-11-01
影响因子：
3.6
通讯作者：
ADAMS, BM
中科院分区：
文献类型：
--
作者：
ADAMS, TE;CUMMING, S;ADAMS, BM
在连续 GnRH 刺激期间和之后测定去势大鼠的促性腺激素反应性、黄体生成素 (LH) 的血清和组织水平以及促性腺激素释放激素 (GnRH) 受体的组织浓度。腹膜内放置含有GnRH的渗透微型泵96小时，建立了GnRH递送速率(1μg/h)，其导致稳定的GnRH血清水平(500-700pg/ml)。 LH分泌量在6小时内增加8倍；然而，即使持续 GnRH 刺激，血清 LH 也会在 24 小时内恢复到治疗前水平。治疗开始后 48 小时内，LH 的组织浓度下降，但 96 小时后恢复水平。 GnRH 受体的组织水平在治疗的前 6 小时内保持升高，但在 24 小时内降低了 60%，并在治疗期间保持低迷状态。治疗开始后 48 小时和 96 小时，促性腺激素反应性分别降低 50% 和 90%。去除 GnRH 递送载体导致 GnRH 从血清中快速消失。在微型泵移除后 6 小时内，LH 循环水平显着降低 (75%)，LH 组织水平和 GnRH 受体浓度增加 2 倍。尽管 GnRH 受体的组织浓度在微型泵移除后 48 小时内恢复到治疗前水平，但即使在连续 GnRH 刺激停止后 96 小时，基础 LH 分泌和促性腺激素反应性仍然受到抑制。这些数据表明 1) GnRH 及其受体“下调”，2) 促性腺激素反应性并不一定与受体浓度相关，3) 过度刺激后的脱敏代表了针对受体后基因座的效应。
Gonadotrope responsiveness, serum and tissue levels of luteinizing hormone (LH), and tissue concentration of gonadotropin-releasing hormone (GnRH) receptors in ovariectomized rats were determined during and after continuous GnRH stimulation. Intraperitoneal placement of GnRH-containing osmotic minipumps for 96 h established a rate of GnRH delivery (1 .mu.g/h) that resulted in stable serum levels of GnRH (500-700 pg/ml). Secretion of LH increased 8-fold within 6 h; however, serum LH returned to pretreatment levels by 24h, even with continued GnRH stimulation. Tissue concentration of LH was depressed within 48 h of intitiation of treatment but levels were restored by 96 h. Tissue levels of GnRH receptor remained elevated during the first 6 h of treatment but were reduced by 60% within 24 h and remained depressed for the duration of treatment. Gonadotrope responsiveness 48 h and 96 h after initiation of treatment was reduced by 50% and 90%, respectively. Removal of the GnRH delivery vehicle resulted in rapid disappearance of GnRH from serum. Dramatic reduction (75%) in circulating levels of LH, and a 2-fold increase in tissue levels of LH and in GnRH receptor concentration were noted within 6 h of minipump removal. Although tissue concentration of GnRH receptor returned to pretreatment levels within 48 h of minipump removal, both basal LH secretion and gonadotrope responsiveness remained depressed even 96 h after cessation of continuous GnRH stimulation. These data indicate that 1) GnRH and "down regulate" its receptor, 2) gonadotrope responsiveness is not obligatorily linked to receptor concentration, and 3) desensitization that follows hyperstimulation represents effects directed at post-receptor loci.