Regulation of pituitary glycoprotein alpha-subunit secretion after administration of a luteinizing hormone-releasing hormone antagonist in normal men.
Pituitary glycoprotein hormones are composed of two different subunits, the alpha- and beta-subunits. The alpha-subunit is common to all FSH, LH, and TSH, while the beta-subunit is specific for each of these hormones. We studied the effects of a potent LHRH antagonist on alpha-subunit and LH secretion in normal men. The LHRH antagonist Nal-Glu, ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA) ,Ala10]LHRH), was given (10 mg daily) as one injection of 5 mg every 12 h. Blood samples were drawn every 24 h, and on days 1 and 7 a day curve was established by drawing hourly blood samples for 26 h. Mean serum alpha-subunit levels decreased progressively (P less than 0.001) from 2.9 +/- 0.49 micrograms/L at baseline to a nadir of 1.4 +/- 0.27 micrograms/L on day 8. In contrast, mean immunoreactive LH (IR-LH) levels decreased rapidly from 3.2 +/- 0.6 U/L at baseline to 0.9 +/- 0.08 U/L on day 2 and remained suppressed (P less than 0.001) throughout the treatment period. On day 1 after the administration of Nal-Glu mean alpha-subunit levels decreased, although not significantly (P = 0.054), from 3.0 +/- 0.6 micrograms/L at baseline to a nadir of 2.0 +/- 0.3 micrograms/L at 17 h. alpha-Subunit remained at this level for the remainder of day 1. On day 7, however, the baseline serum alpha-subunit level was 1.5 +/- 0.3 micrograms/L, significantly suppressed (P less than 0.01) compared to the level on day 1, and no further decrease was seen after administration of Nal-Glu. IR-LH on day 1 before the first injection of 5 mg Nal-Glu was 3.5 +/- 0.8 U/L. Then, IR-LH levels decreased significantly (P less than 0.001) to a nadir of 0.9 +/- 0.1 U/L and remained at this level throughout day 1. IR-LH levels on day 7 were at or below 1.0 U/L throughout the sampling period. These results indicate that alpha-subunit secretion can be partially suppressed after chronic administration of a LHRH antagonist. Furthermore, LH serum levels dissociate from those of pituitary glycoprotein alpha-subunit after administration of LHRH antagonist analogs.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J
J
Lindner
J E
JE
Rivier
W W
WW
Vale
S N
SN
Pavlou
D000328:Adult; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology
D015292:Glycoprotein Hormones, alpha Subunit; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone