Luteolysis is linked to luteinizing hormone-induced depletion of adenosine triphosphate in vivo.
An elevation of ATP levels in luteal cells markedly enhances their response to gonadotropin. In contrast, depletion of ATP in all cells leads to a series of interrelated events that produces irreversible cell injury. Since the corpus luteum has a transient existence, functional regression and involution of this gland play a fundamental role in the regulation of reproduction. The objective of the present studies was to evaluate whether the luteal ATP content may be regulated in an endocrine fashion and whether luteolysis may be linked to depletion of ATP in the corpus luteum in vivo. The present studies show that removal of the pituitary, maintenance of luteal function in hypophysectomized rats with PRL, or acute treatment with prostaglandin F2 alpha had no effect on luteal ATP levels. However, LH produced a rapid and marked decrease in adenine nucleotide levels in both intact and hypophysectomized PRL-replaced rats, whereas GTP levels were unaffected. In pituitary-intact rats, this same effect of LH occurred within 5 min, was maximal (40% depletion) within 30 min, and was sustained for many hours. Depletion of ATP by LH was dose dependent and evident with low doses of LH. In addition, a decrease in luteal ATP levels was seen during functional luteolysis in the rat, which was directly related to a rise in the serum levels of LH, but not FSH. In contrast, LH had no effect on ATP depletion in isolated cells prepared from the total luteinized ovary, or in enriched preparations of luteal cells. Thus, the depletion of ATP by LH in vivo appears to be mediated by intraovarian agents of unknown nature. We suggest that the rise in LH levels that follows functional luteolysis, due to reduced negative feedback by progesterone, produces a rapid decrease in luteal ATP levels which induces irreversible cell damage and, ultimately, involution of the corpus luteum. This effect would, presumably, be exacerbated as LH levels rise to maximum at ovulation or until LH receptors become down-regulated.
Soodak
L K
LK
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
MacDonald
G J
GJ
Behrman
H R
HR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D007016:Hypophysectomy; D007700:Kinetics; D007986:Luteinizing Hormone / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D007986:Luteinizing Hormone