Disturbance of follicular development and endocrine reactions induced by the antiovulatory effective progesterone antagonist Onapristone.
The present study was undertaken to investigate whether inhibition of ovulation, which is known to occur after treatment with progesterone antagonists, is due to the effect of high levels of prolactin. Therefore, rats with 4-day cycles were treated with the antiprogestin, Onapristone (ON), once daily starting on the evening of estrus. It was detected that the profile of peripheral prolactin levels during the treatment with ON was not remarkably different from that found in the controls. Furthermore, bromocriptine, a prolactin antagonist, was not able to reverse the antiovulatory potency of ON. It is concluded that the antiovulatory effect of ON might not be related to changes in the level of prolactin. Nevertheless, prolactin levels remained high after the preovulatory surge. Thus, we cannot exclude the possibility that PRL plays a role in the induction of anovulatory cycles observed during long term treatment. In animals treated for the length of one cycle we found that the preovulatory LH surge decreased but it remains questionable whether this contributes to the inhibition of ovulation by ON. Interestingly, basal LH, androgen and estrogen levels were elevated. Accordingly, we favour the idea that LH stimulates the theca interstitial cells to produce excessive amounts of androgens which may be aromatized into estrogens. These high levels of androgens and estrogens may contribute to the antiovulatory mechanism of ON by disturbing physiological follicular development. In fact, a morphometrical analysis revealed an increase in the volume density of late tertiary follicles. The increased progesterone levels may also be related to high basal LH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Schubert
C
C
Forschungslaboratorien der Schering AG Berlin, Germany.
Nishino
Y
Y
Michna
H
H
D000735:Androstenedione / Q000097:blood; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006067:Gonanes / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013739:Testosterone / Q000097:blood
D006067:Gonanes; D001971:Bromocriptine; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C053238:onapristone; D003345:Corticosterone