Erickson G F, Kokka S, Rivier C
Department of Reproductive Medicine, University of California-San Diego, La Jolla 92093-0674, USA.
Endocrinology. 1995 Nov;136(11):4804-13. doi: 10.1210/endo.136.11.7588210.
In the rat ovary, follicle cells produce and respond to activin, but as yet, the functional significance of the autocrine/paracrine effects of ovarian activin remains equivocal. To assess the effects of activin on folliculogenesis, normal cycling female rats were injected once every 8 h over a 40-h period with recombinant human activin A (120 micrograms/kg) beginning at 1300 h on estrus (day 1 of treatment). A total of 10 rats were injected with activin in 2 separate experiments. On days 3 and 4 of treatment, blood was obtained for hormone measurements, and the ovaries were removed for histology. Follicle counts were performed in 1 ovary from 3 representative animals in each treatment group. All antral (Graafian) follicles 300 microns or more in diameter were measured and classified as healthy or atretic based on the number of pyknotic nuclei in the largest cross-section. On day 3, all rats were in diestrus (diestrous day 2). After 3 days of activin administration, serum levels of estradiol were increased 200%, progesterone levels were decreased 67%, and FSH levels were unchanged compared with those in matched controls. By day 4 (i.e. 1 day after the last injection), no changes in the levels of these hormones were observed. Injection of activin for 3 days did not change the total number of antral follicles per ovary (control, 41.3 +/- 4.9; activin, 43.7 +/- 3.9); however, activin significantly increased the total number of atretic follicles (control, 69%; activin, 92%). Morphometric analysis of the ovaries removed on day 3 showed a marked increase (2-fold) in the number of large follicles, but most (89%) were atretic. Follicle counts suggested that the additional large follicles may have come from the pool of healthy small follicles. Histological studies showed that some of the day 3 activin-treated follicles had initiated ovulation. On day 4, control and activin-treated animals were at proestrus and estrus, respectively. Therefore, activin shortened the estrous cycle by 1 day. Little or n change in the follicle populations was observed in day 4 control ovaries. Interestingly, however, in 2 of the 3 activin-treated animals, 1 set of large follicles had ovulated (12 +/- 1 expanded egg cumulus complexes/oviduct), and another set (13 +/- 2) was just about to rupture. The activin-exposed oocytes (tubal and follicular) appeared arrested in metaphase I. After ovulation, activin-treated follicles developed into typical corpora lutea. No ovulations were found in control animals.(ABSTRACT TRUNCATED AT 400 WORDS)
在大鼠卵巢中，卵泡细胞产生并对激活素作出反应，但迄今为止，卵巢激活素自分泌/旁分泌作用的功能意义仍不明确。为了评估激活素对卵泡发生的影响，从发情期（治疗第1天）13:00开始，正常发情周期的雌性大鼠在40小时内每隔8小时注射一次重组人激活素A（120微克/千克）。在2个独立实验中，共有10只大鼠注射了激活素。在治疗的第3天和第4天，采集血液进行激素测量，并摘除卵巢进行组织学检查。对每个治疗组中3只代表性动物的1个卵巢进行卵泡计数。测量所有直径300微米或更大的窦状（格拉夫卵泡）卵泡，并根据最大横切面中固缩核的数量将其分类为健康或闭锁。在第3天，所有大鼠处于间情期（间情期第2天）。给予激活素3天后，与配对对照组相比，血清雌二醇水平升高了200%，孕酮水平降低了67%，促卵泡激素水平未发生变化。到第4天（即最后一次注射后1天），未观察到这些激素水平的变化。注射激活素3天并未改变每个卵巢中窦状卵泡的总数（对照组，41.3±4.9；激活素组，43.7±3.9）；然而，激活素显著增加了闭锁卵泡的总数（对照组，69%；激活素组，92%）。对第3天摘除的卵巢进行形态计量分析显示，大卵泡数量显著增加（2倍），但大多数（89%）为闭锁卵泡。卵泡计数表明，额外的大卵泡可能来自健康小卵泡池。组织学研究表明，第3天接受激活素治疗的一些卵泡已开始排卵。在第4天，对照组和激活素治疗组的动物分别处于动情前期和发情期。因此，激活素使发情周期缩短了1天。在第4天的对照卵巢中，卵泡数量几乎没有变化。然而，有趣的是，在3只接受激活素治疗的动物中的2只，一组大卵泡已经排卵（12±1个扩张的卵丘复合体/输卵管），另一组（13±2个）即将破裂。暴露于激活素的卵母细胞（输卵管和卵泡内的）似乎停滞在第一次减数分裂中期。排卵后，接受激活素治疗的卵泡发育成典型的黄体。在对照动物中未发现排卵情况。（摘要截断于400字）
