ACTIVIN CAUSES PREMATURE SUPEROVULATION

被引:26
作者
ERICKSON, GF [1 ]
KOKKA, S [1 ]
RIVIER, C [1 ]
机构
[1] SALK INST BIOL STUDIES, CLAYTON FDN LABS PEPTIDE BIOL, LA JOLLA, CA 92037 USA
关键词
D O I
10.1210/en.136.11.4804
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu g/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 mu m 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 no 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. We conclude that multiple injections of activin A into adult cycling rats leads to premature superovulation of immature eggs from large follicles, many of which appear atretic.
引用
收藏
页码:4804 / 4813
页数:10
相关论文
共 46 条
[21]   ACTIVIN RECEPTORS AND CELLULAR SIGNALING BY THE RECEPTOR SERINE KINASE FAMILY [J].
MATHEWS, LS .
ENDOCRINE REVIEWS, 1994, 15 (03) :310-325
[22]   RAPID CHANGES IN THE EXPRESSION OF INHIBIN ALPHA-SUBUNITS, BETA-A-SUBUNITS, AND BETA-B-SUBUNITS IN OVARIAN CELL-TYPES DURING THE RAT ESTROUS-CYCLE [J].
MEUNIER, H ;
CAJANDER, SB ;
ROBERTS, VJ ;
RIVIER, C ;
SAWCHENKO, PE ;
HSUEH, AJW ;
VALE, W .
MOLECULAR ENDOCRINOLOGY, 1988, 2 (12) :1352-1363
[23]   PERIOVULATORY CHANGES IN THE EXPRESSION OF INHIBIN ALPHA-SUBUNIT BETA-A-SUBUNIT, AND BETA-B-SUBUNIT IN HORMONALLY INDUCED IMMATURE FEMALE RATS [J].
MEUNIER, H ;
ROBERTS, VJ ;
SAWCHENKO, PE ;
CAJANDER, SB ;
HSUEH, AJW ;
VALE, W .
MOLECULAR ENDOCRINOLOGY, 1989, 3 (12) :2062-2069
[24]   DEVELOPMENT-RELATED EFFECTS OF RECOMBINANT ACTIVIN ON STEROID-SYNTHESIS IN RAT GRANULOSA-CELLS [J].
MIRO, F ;
SMYTH, CD ;
HILLIER, SG .
ENDOCRINOLOGY, 1991, 129 (06) :3388-3394
[25]   DIFFERENTIAL CONTROL OF ACTIVIN, INHIBIN AND FOLLISTATIN PROTEINS IN CULTURED RAT GRANULOSA-CELLS [J].
MIYANAGA, K ;
ERICKSON, GF ;
DEPAOLO, LV ;
LING, N ;
SHIMASAKI, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 194 (01) :253-258
[26]   EFFECT OF ACTIVIN ON LUTEINIZING HORMONE-HUMAN CHORIONIC-GONADOTROPIN RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN GRANULOSA-CELLS [J].
NAKAMURA, K ;
NAKAMURA, M ;
IGARASHI, S ;
MIYAMOTO, K ;
ETO, Y ;
IBUKI, Y ;
MINEGISHI, T .
ENDOCRINOLOGY, 1994, 134 (06) :2329-2335
[27]   EFFECT OF AN ACTIVIN-A ON FOLLICLE-STIMULATING-HORMONE (FSH) RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS AND FSH RECEPTOR EXPRESSIONS IN CULTURED RAT GRANULOSA-CELLS [J].
NAKAMURA, M ;
MINEGISHI, T ;
HASEGAWA, Y ;
NAKAMURA, K ;
IGARASHI, S ;
ITO, I ;
SHINOZAKI, H ;
MIYAMOTO, K ;
ETO, Y ;
IBUKI, Y .
ENDOCRINOLOGY, 1993, 133 (02) :538-544
[28]  
NAKAMURA T, 1992, J BIOL CHEM, V267, P16385
[29]   EFFECTS OF UNILATERAL OVARIECTOMY ON OVULATION AND CYCLE LENGTH IN 4-DAY AND 5-DAY CYCLING RATS [J].
PEPPLER, RD ;
GREENWAL.GS .
AMERICAN JOURNAL OF ANATOMY, 1970, 127 (01) :1-&
[30]   THE CHRONIC INTRACEREBROVENTRICULAR INFUSION OF INTERLEUKIN-1-BETA ALTERS THE ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS OF CYCLING RATS .1. EFFECT ON LHRH AND GONADOTROPIN BIOSYNTHESIS AND SECRETION [J].
RIVEST, S ;
LEE, S ;
ATTARDI, B ;
RIVIER, C .
ENDOCRINOLOGY, 1993, 133 (06) :2424-2430