Effects of chronic GnRH analogue administration on gonadotrophin and alpha-subunit secretion in post-menopausal women.
OBJECTIVE
To investigate in detail the regulation of LH, FSH, and alpha-subunit secretion by a GnRH agonist analogue under physiological conditions of gonadotrophin elevation.


METHODS
Six normal healthy post-menopausal women.


METHODS
Subjects were given D-Trp6-Pro9-Net-GnRH (GnRHa), 32 micrograms/kg, subcutaneously, daily for 24 days. On days 1, 2, 3, 4, 7, 11, 14, 17, 21, and 24, blood samples before and after GnRHa injection were taken. Sampling was continued off GnRHa twice a week for 4 weeks and then on days 66, 76, and 98. GnRH tests (100 micrograms i.v.) were performed on days 0, 24, and 98.


METHODS
All serum samples were analysed for LH, FSH, and alpha-subunit levels.


RESULTS
LH and FSH levels reached a maximum on day 2 after which there was a steady decline to day 24. LH did not begin to rise again until day 44 (20 days off GnRHa), then rose steadily. FSH began to rise earlier, on day 34 (10 days off GnRHa). alpha-Subunit levels also showed maximum elevation on day 2 but remained equally elevated throughout the period of GnRHa administration and then fell rapidly to baseline by day 34. LH, FSH, and alpha-subunit responses to i.v. GnRH were absent on day 24 and were equivalent to baseline on day 98.


CONCLUSIONS
We conclude that there is a striking dissociation in the regulation of gonadotrophin and alpha-subunit secretion in response to GnRHa in normal post-menopausal women. Gonadotrophin secretion is profoundly suppressed during GnRHa administration and recovers only after a long delay post-treatment, while alpha-subunit is markedly stimulated and recovers rapidly. The difference between this pattern and that seen in patients with pituitary tumours could be useful for diagnosis.
Oppenheim
D S
DS
Neuroendocrine Unit, Massachusetts General Hospital, Boston 02114.
Bikkal
H
H
Crowley
W F
WF
Klibanski
A
A
D000368:Aged; D003864:Depression, Chemical; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D015292:Glycoprotein Hormones, alpha Subunit; D006065:Gonadotropins, Pituitary; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C019176:Tryptal; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone