EFFECTS OF GONADOTROPIN-RELEASING-HORMONE ANTAGONIST AND AGONIST ON THE PULSATILE RELEASE OF GONADOTROPINS AND ALPHA-SUBUNIT IN POSTMENOPAUSAL WOMEN

被引:30
作者
COUZINET, B
LAHLOU, N
THOMAS, G
THALABARD, JC
BOUCHARD, P
ROGER, M
SCHAISON, G
机构
[1] HOP BICETRE,SERV ENDOCRINOL & MALAD REPROD,F-94275 LE KREMLIN BICETR,FRANCE
[2] FDN RECH HORMONOL,F-94268 FRESNES,FRANCE
关键词
D O I
10.1111/j.1365-2265.1991.tb00328.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues. DESIGN AND PATIENTS Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women. MEASUREMENTS A baseline study of pulsatile LH, FSH and free alpha-subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal-Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D-Trp6 GnRH (3.75 mg) in the same women. RESULTS The baseline sampling period showed synchronous pulses of LH and free alpha-subunit. The antagonist NalGlu decreased plasma LH (71%) and free alpha-subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free alpha-subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free alpha-subunit from 1.66 +/- 0.01 to 5.06 +/- 0.02-mu-g/l (205%). The pulsatile secretory patterns of both LH and free alpha-subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%). CONCLUSIONS The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free alpha-subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free alpha-subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free alpha-subunit by GnRH.
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页码:477 / 483
页数:7
相关论文
共 28 条
[1]   MECHANISMS OF GONADOTROPIN-RELEASING-HORMONE AGONIST ACTION IN THE HUMAN MALE [J].
BHASIN, S ;
SWERDLOFF, RS .
ENDOCRINE REVIEWS, 1986, 7 (01) :106-114
[2]   GONADOTROPIN-RELEASING-HORMONE (GNRH) AGONISTS AND GNRH ANTAGONISTS DO NOT ALTER ENDOGENOUS GNRH SECRETION IN SHORT-TERM CASTRATED RAMS [J].
CARATY, A ;
LOCATELLI, A ;
DELALEU, B ;
SPITZ, IM ;
SCHATZ, B ;
BOUCHARD, P .
ENDOCRINOLOGY, 1990, 127 (05) :2523-2529
[3]   GONADOTROPIN-RELEASING HORMONE - ITS ACTIONS AND RECEPTORS [J].
CLAYTON, RN .
JOURNAL OF ENDOCRINOLOGY, 1989, 120 (01) :11-19
[4]   COMPARATIVE EFFECTS OF CYPROTERONE-ACETATE OR A LONG-ACTING GONADOTROPIN-RELEASING-HORMONE AGONIST IN POLYCYSTIC OVARIAN DISEASE [J].
COUZINET, B ;
LESTRAT, N ;
BRAILLY, S ;
SCHAISON, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 63 (04) :1031-1035
[5]   THERAPEUTIC USE OF PITUITARY DESENSITIZATION WITH A LONG-ACTING LHRH AGONIST - A POTENTIAL NEW TREATMENT FOR IDIOPATHIC PRECOCIOUS PUBERTY [J].
CROWLEY, WF ;
COMITE, F ;
VALE, W ;
RIVIER, J ;
LORIAUX, DL ;
CUTLER, GB .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1981, 52 (02) :370-372
[6]   THE FREQUENCY OF GONADOTROPIN-RELEASING-HORMONE STIMULATION DIFFERENTIALLY REGULATES GONADOTROPIN SUBUNIT MESSENGER RIBONUCLEIC-ACID EXPRESSION [J].
DALKIN, AC ;
HAISENLEDER, DJ ;
ORTOLANO, GA ;
ELLIS, TR ;
MARSHALL, JC .
ENDOCRINOLOGY, 1989, 125 (02) :917-924
[7]   SUSTAINED INHIBITORY ACTIONS OF A POTENT ANTAGONIST OF GONADOTROPIN-RELEASING-HORMONE IN POSTMENOPAUSAL WOMEN [J].
DAVIS, MR ;
VELDHUIS, JD ;
ROGOL, AD ;
DUFAU, ML ;
CATT, KJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1987, 64 (06) :1268-1274
[8]   A NON-GAUSSIAN MODEL FOR TIME-SERIES WITH PULSES [J].
DIGGLE, PJ ;
ZEGER, SL .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1989, 84 (406) :354-359
[9]   SUPPRESSION OF POSTMENOPAUSAL OVARIAN STEROIDOGENESIS WITH THE LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST GOSERELIN [J].
DOWSETT, M ;
CANTWELL, B ;
LAL, A ;
JEFFCOATE, SL ;
HARRIS, AL .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1988, 66 (04) :672-677
[10]   A LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST DECREASES BIOLOGICAL-ACTIVITY AND MODIFIES CHROMATOGRAPHIC BEHAVIOR OF LUTEINIZING-HORMONE IN MAN [J].
EVANS, RM ;
DOELLE, GC ;
LINDNER, J ;
BRADLEY, V ;
RABIN, D .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 73 (01) :262-266