Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and alpha-subunit in postmenopausal women.
OBJECTIVE
The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues.


METHODS
Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women.


METHODS
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 Nal-Glu 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 micrograms/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.
Couzinet
B
B
Service d'Endocrinologie et des maladies de la Reproduction, Hopital Bicêtre, France.
Lahlou
N
N
Thomas
G
G
Thalabard
J C
JC
Bouchard
P
P
Roger
M
M
Schaison
G
G
D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D012636:Secretory Rate / Q000187:drug effects; D017329:Triptorelin Pamoate
D015292:Glycoprotein Hormones, alpha Subunit; D006065:Gonadotropins, Pituitary; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone