Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) in Modulation of Insulin Gene Expression for Healthy Egg Production in Female

Abstract

Egg health is one of the cornerstone of healthy fertility. To shield of a safe pregnancy, healthy egg production is ineluctable. Reproduction and metabolism are tightly connected and reciprocally regulated. Insulin plays a role in regulating reproduction and perform as a major signal linking metabolism and reproductive status. Insulin acts as a co-gonadotropin at the level of the ovary which enhances steroidogenic responses to gonadotropins. Most of the insulin pathways are active in the ovary and their ability to interact with each other and also with FSH and LH signaling pathways enables insulin to exert direct modulating influences on ovarian function. In this review, a modulatory effect of insulin gene expression on follicle stimulating hormone (FSH) and luteinizing hormone (LH) has been shown that could have been playing role on healthy fertility. The process is regulated by Akt pathway which is the signal transduction pathway of living cell in the ovary; where key proteins are Phosphatidylinositol 3 kinase (PI3K) and protein kinase B (Akt). Insulin signaling through Akt and FOXOI can enhance FSH and LH stimulated steroidogenesis. FSH and LH acting via mTOR/ERK can enhance cell proliferation and protein synthesis. When insulin binds to its receptor, it activates b-subunit tyrosin kinase which enhance PI3K activation. Then DNA is synthesized through p21 Ras and MAPK. Actually, Akt can not directly activate mTOR, only Rheb can. Inside the cell the Rheb is inactivated or turned off by Tsc1 and Tsc2. Akt inhibits this Tsc timers, then Rheb is free which regulate mTOR. Inositol glycans are also generated by insulin signaling pathway which mediate steroidogenic effects of insulin action. On the other hand, there are some negative regulators which are used the maintenance of dormancy of primordial follicles like PTEN, Tsc1, Tsc2, 4EBP1 etc. So there is a harmonic relationship among insulin, FSH and LH which guides to fabricate fertile follicular progress as well as manufacture of healthy egg.