Leptin receptor stimulation in late pregnant mouse uterine tissue inhibits spontaneous contractions by increasing NO and cGMP. (January 2021)

• Record Type: Journal Article
• Authors: Srinivasan, G.; Parida, Subhashree; Pavithra, S.; Panigrahi, Manjit; Sahoo, Monalisa; Singh, Thakur Uttam; Madhu, C.L.; Manickam, Kesavan; Shyamkumar, T.S.; Kumar, Dinesh; Mishra, Santosh K.
• Is Part Of: Cytokine. Volume 137(2021)
• Publication Date: 2021-01
• Subjects: Leptin -- Leptin receptors -- JAK2/3 -- ERK1/2 -- Nitric oxide -- cGMP; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155341
• Languages: English
• ISSNs: 1043-4666

Abstract

Abstract: The adipokine, leptin exerts inhibitory effect on both spontaneous and oxytocin-induced contractions in myometrium. However, the mechanisms involved in leptin-induced effect are not clear. In the present study, we studied the altered characteristics of uterine contractions in the presence of leptin and the possible mechanisms of its effect in late pregnant (18.5 day) mouse uterus. We conducted functional, biochemical and molecular biology studies to demonstrate the mechanism of leptin-induced response. Leptin exerted an inhibitory response (Emax 40.5 ± 3.99%) on basal uterine contractions. The extent of inhibition was less than that obtained with known uterine relaxants, salbutamol (Emax 103 ± 8.66%) and BRL-37344 (Emax 84.79 ± 8.12%). Leptin-induced uterine response was inhibited by leptin receptor antagonist SHLA and JAK-STAT pathway inhibitor, AG-490. The relaxant response was also subdued by NO-cGMP-PK-G pathway blockers L-NAME, 1400W, ODQ and KT-5823. Further, leptin enhanced the levels of NO and cGMP in uterine tissues. Also, SHLA, AG-490 and a combination of 1400 W and L-NAME prevented leptin-induced increase in NO. Similar effect was observed on cGMP levels in presence of leptin and SHLA. However, leptin did not influence CaCl2 -induced response in potassium-depolarized tissues. We also detected leptin receptor protein in late pregnant mouse uterus located in endometrial luminal epithelium and myometrial layers. Real-time PCR studies revealed significantly higher expression of short forms of the receptor (ObRa and ObRc) in comparison to the long form (ObRb). In conclusion, the results of the present study suggest that leptin inhibits mouse uterine contraction by stimulating short forms of the leptin receptors and activating NO pathway in a JAK-STAT-dependent manner.