[Regulation of follicular luteinization by an agonist of gonadotropin-releasing hormone (GnRH)].
Long treatments with GnRH agonist are used in patients to suppress the endogenous secretion of gonadotropins, however; these analogs have a direct effect on the ovary. The aim of this work was to study the in vivo effect of the GnRH analogue, leuprolide acetate (LA) on ovarian steroidogenesis and apoptosis mechanisms. LA (1 microgram/rat/day) was injected to PMSG/hCG superovulated rats. Corpora lutea were isolated by microdissection and incubated (4/0.5 ml) during 3 h with LH (10 ng/ml) or dibutyryl cAMP (dcAMP 1 mM). Progesterone production was measured observing in LA treated rats a decrease in basal and LH stimulated values (Basal = Control C: 96.6 +/- 9.6; LA: 22.9 +/- 2.8; LH = C: 145.7 +/- 4.9; LA: 23.6 +/- 2.0 ng/ml, p < 0.001). In contrast, dcAMP stimulated significantly both groups (C: 153.9 +/- 11.8; LA: 83.15 +/- 8.2). cAMP production was lower in LA corpora lutea and LH was not able to stimulate them (Basal = C: 7.29 +/- 1.6; LA: 1.17 +/- 0.6; LH = C: 13.2 +/- 0.4; LA: 2.5 +/- 0.4 ng/ml, p < 0.01). Corpus luteum of both groups showed similar protein content. On the other hand, taking into account that in ovarian histological slides of LA treated rats we observed more atresic follicles and less corpora lutea, we determined the amount of apoptotic cells. The criterion used was the presence of apoptotic bodies and nuclear chromatin aggregated in dense masses beneath the nuclear envelope. An increase of apoptotic cells in the LA group ovaries was detected. This result was confirmed by immunohistochemical technics (TUNEL). It was concluded that LA treatment produces in ovarian cells a failure in the LH receptor-adenilate cyclase system and an increase in cellular apoptosis.
Andreu
C
C
Instituto de Biología y Medicina Experimental-CONICET-Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Parborell
F
F
Vanzulli
S
S
Tesone
M
M
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D016729:Leuprolide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018931:Antineoplastic Agents, Hormonal; D016729:Leuprolide