Luteolysis Is Linked to Luteinizing Hormone-Induced Depletion of Adenosine Triphosphatein Vivo*

Abstract

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.

Purinergic signalling in the reproductive system in health and disease

“…Luteal cell ATP is rapidly depleted by LH. This appears to be a physiological event as a result of cells undergoing apoptosis (i.e., luteolysis) at the end of the pseudopregnant cycle [382].…”

31P NMR studies of phosphate metabolism in the ovulatory process induced by gonadotropins in perfused rabbit ovary

“…Billig and Rosberg 3 reported that ATP levels in rat granulosa cells are markedly depressed by gonadotropins, and the gonadotropin-induced decrease in ATP can be explained by its increased consumption and/or decreased production. Soodak et al 4 reported that luteinizing hormone depletes luteal ATP levels in luteinized ovaries, and suggested that ovulation causes depletion of luteal ATP levels to ensure irreversible regression and eventual death of the corpora lutea. The findings of a decrease in ATP level during the infusion of gonadotropin are in agreement with the results of some investigators.…”

“…It has been demonstrated that stimulation with follicle stimulating hormone (FSH) or luteinizing hor-mone (LH) depresses the level of ATP in granulosa cells or luteinized ovaries. 3,4 Patwardhan and Lanthier 5 reported that both LH and human chorionic gonadotropin (HCG) induce a rapid increase in ovarian cyclic adenosine 3',5'-monophosphate (cAMP) concentrations. Holmes et al 6 suggested that cAMP is a sufficient signal to initiate the ovulatory process through adenylate cyclase activation.…”

Purinergic signalling in endocrine organs

“…LH rapidly depletes luteal cell ATP, which appears to be a physiological action, since it occurs during functional luteolysis at the end of the pseudopregnant cycle [501]. The authors suggest that during functional luteolysis, the rising levels of LH that occurs during follicular development and ovulation cause depletion of luteal ATP levels to ensure irreversible regression and eventual death of the corpora lutea of the previous cycle.…”