Relative Importance of the Adenohypophyseal and Gonadal Sites of Inhibitory Action of LHRH Agonists

• Published in: Biology of reproduction Vol. 24; no. 4; pp. 889 - 901
• Main Authors: Séguin, Carl, Bélanger, Alain, Cusan, Lionel, Pelletier, Georges, Reeves, Jerry J., Lefebvre, Fleur-Ange, Kelly, Paul A., Labrie, Fernand
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01-05-1981
• Subjects: Animals; Buserelin; Depression, Chemical; Female; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - pharmacology; Male; Ovary - drug effects; Ovary - metabolism; Pituitary Gland, Anterior - physiology; Rats; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Receptors, FSH; Receptors, LH; Receptors, Prolactin; Testis - drug effects; Testis - metabolism
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod24.4.889

Assessment of the role of endogenous LH release and direct gonadal action of LHRH agonists in
the loss of gonadal LH receptors induced by treatment with gonadotropin-releasing peptides was
first made by comparing the effect of single administration of 1 µg of [D-Ala 6 , des-Gly-NH 2 10 ]-LHRH ethylamide, [D-Ala 6 ] LHRH-EA, 12 h before or immediately after hypophysectomy
(HYPOX) on LH receptor levels measured 48 h after surgery in male and female adult rats. While
administration of the LHRH agonist before HYPOX leads to a 50% loss of testicular LH receptors,
only a 20% decrease is seen in HYPOX animals, thus suggesting a predominant role of endogenous
LH release in the desensitization process in male animals. Treatment with increasing doses (1 to
100 ng/day) of another LHRH agonist, [D-Ser(TBU) 4 ] LHRH-EA, causes a 90% loss of testicular
LH receptors in intact rats at the highest dose used (100 ng daily for 9 days) while the same
treatment decreases LH receptors by only 35% in HYPOX animals. As measured by the steroidogenic response to 10 µg oLH in vivo,
while treatment of intact animals with [D-Ser(TBU) 6 ] LHRH-EA leads to a marked blockage of the testicular steroidogenic pathway at the level of 17-hydroxylase and 17,20-desmolase
activities with a corresponding increase of 5α-reductase activity, minimal
or no signs of changes of enzymatic activity are seen after identical treatment in HYPOX animals.
Chronic treatment (1 month) with the LHRH agonist in intact rats leads to degenerative changes of
the seminiferous tubules, while no effect is observed in HYPOX animals, thus suggesting the
essential role of the pituitary gland. Moreover, adrenalectomy does not influence the inhibitory
effect of treatment with LHRH agonists on the loss of testicular LH receptors in HYPOX animals,
thus eliminating the role of the adrenals in the action of LHRH agonists. Contrary to the results
obtained in male animals, single administration of the LHRH agonist in female rats has similar
inhibitory effects on ovarian gonadotropin receptors when administered either before or after
hypophysectomy. Moreover, treatment with increasing doses of [D-Ser(TBU) 6 ] LHRH-EA leads to
a similar inhibition of ovarian LH receptor levels in intact and HYPOX female animals. The present
data show that LHRH agonist-induced endogenous LH release plays a predominant role in the
desensitizing effect of treatment with LHRH agonists on testicular LH receptors and steroidogenesis as well as on inhibition
of spermatogenesis; in the female, the direct gonadal effect, at least
on LH and FSH receptors, appears to play a more important role than in male animals.