Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells

Abstract

Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFR) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized to the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production by luteal cells obtained at mid-late and late luteal phases but did not decrease progesterone production by granulosa or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.

Thrombospondin 1 (THBS1) Promotes Follicular Angiogenesis, Luteinization, and Ovulation in Primates

“…PGF2α increases THBS1 and THBS2 mRNAs in the bovine corpus luteum, where THBS1 plays a role in luteal regression (5). PGF2α receptors present in granulosa cells of the primate ovulatory follicle and young corpus luteum are not capable of signal transduction (26), so the PGF2α pathway is not available to regulate expression of thrombospondins, despite elevated follicular PGF2α levels. PGF2α receptors in primate luteal cells can mediate PGF2α signals later in the luteal phase (26).…”

“…PGF2α receptors present in granulosa cells of the primate ovulatory follicle and young corpus luteum are not capable of signal transduction (26), so the PGF2α pathway is not available to regulate expression of thrombospondins, despite elevated follicular PGF2α levels. PGF2α receptors in primate luteal cells can mediate PGF2α signals later in the luteal phase (26). While prostaglandins are not a key regulators of thrombospondin protein levels in the primate ovulatory follicle, prostaglandins may regulate thrombospondin expression and activity in the primate corpus luteum, especially during luteal regression.…”

Prostaglandin F2α Facilitates Hepatic Glucose Production Through CaMKIIγ/p38/FOXO1 Signaling Pathway in Fasting and Obesity

“…Prostaglandin (PG) F 2a is a bioactive lipid metabolite of arachidonic acid produced through the sequential reaction of cyclooxygenases and PGF synthase. PGF 2a exerts a wild range of pathological and physiological functions, including reproduction (8), blood pressure (9), and bone remodeling (10), by binding to its receptor (F-prostanoid [FP]). Experimental and clinical studies showed that PGF 2a is involved in different inflammatory conditions, including rheumatic diseases, asthma, atherosclerosis, ischemia-reperfusion, septic shock, and obesity (11).…”

Coral platy fish Xiphophorus maculatus hormonal induction to improve mass spawning efficiency

“…Based on this result, the administration of oxytocin and PGF2α hormones can increase the birth process stimulation in coral platy fish broodstock, although the best performance was obtained from the administration of PGF2α hormone as increased by 169% compared to control. The PGF2α hormone is often used in animals based on the principle of the hormone administration which can lyse or degrade the corpus luteum followed by decreased progesterone secretion that causes reproductive cycle alteration (Kim et al, 2015;Plewes et al, 2020).…”