Duello T M, Nett T M
Mol Cell Endocrinol. 1980 Jul;19(1):101-12. doi: 10.1016/0303-7207(80)90034-9.
Uptake and retention of GnRH by pituitary was compared to that of GnRH-ethylamide (GnRH-EA) and D-Ala6-GnRH-ethylamide (D-Ala6-GnRH-EA) to determine if differences in these parameters might partially account for the increased biopotency of these superactive analogs. Ovariectomized estrogen/progesterone-treated rats were given an intracarotid injection of either 125I-labeled GnRH, -GnRH-EA, or -D-Ala6-GnRH-EA. Maximum uptake occurred at 2 min for GnRH (8000 cpm/pit), 5 min for GnRH-EA (10 000 cpm/pit), and 45 min for D-Ala6-GnRH-EA (24 000 cpm/pit). Thereafter pituitary content decreased out to 1, 2, and 4 h, resp. Specific uptake of all 3 peptides was shown autoradiographically to be restricted only to immunostained gonadotrophs with the silver grains being localized intracellularly at all time points studied. Serum concentrations of LH increased in response to all 3 peptides in proportion to their uptake and did not begin to decrease until after maximum uptake of each peptide had occurred. Thus, the extent of uptake and length of retention of these peptides in the pituitary correlate well with their relative biopotencies, D-Ala6-GnRH-EA greater than GnRH-EA greater than GnRH.
将垂体对促性腺激素释放激素（GnRH）的摄取和保留情况与促性腺激素释放激素乙酰胺（GnRH-EA）和D-丙氨酸6-促性腺激素释放激素乙酰胺（D-Ala6-GnRH-EA）进行比较，以确定这些参数的差异是否可能部分解释了这些超活性类似物生物活性增强的原因。对去卵巢并接受雌激素/孕酮处理的大鼠进行颈内注射125I标记的GnRH、GnRH-EA或D-Ala6-GnRH-EA。GnRH在2分钟时摄取量最大（8000计数/分钟·垂体），GnRH-EA在5分钟时摄取量最大（10000计数/分钟·垂体），D-Ala6-GnRH-EA在45分钟时摄取量最大（24000计数/分钟·垂体）。此后，垂体含量分别在1小时、2小时和4小时时下降。放射自显影显示，所有3种肽的特异性摄取仅局限于免疫染色的促性腺激素细胞，在所有研究的时间点，银颗粒都定位于细胞内。血清促黄体生成素（LH）浓度对所有3种肽的反应均与其摄取量成比例增加，直到每种肽摄取量达到最大后才开始下降。因此，这些肽在垂体中的摄取程度和保留时间与其相对生物活性密切相关，D-Ala6-GnRH-EA＞GnRH-EA＞GnRH。
