Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues

Abstract

The role of growth hormone (GH) in human fertility is widely debated with some studies demonstrating improvements in oocyte yield, enhanced embryo quality, and in some cases increased live births with concomitant decreases in miscarriage rates. However, the basic biological mechanisms leading to these clinical differences are not well-understood. GH and the closely-related insulin-like growth factor (IGF) promote body growth and development via action on key metabolic organs including the liver, skeletal muscle, and bone. In addition, their expression and that of their complementary receptors have also been detected in various reproductive tissues including the oocyte, granulosa, and testicular cells. Therefore, the GH/IGF axis may directly regulate female and male gamete development, their quality, and ultimately competence for implantation. The ability of GH and IGF to modulate key signal transduction pathways such as the MAP kinase/ERK, Jak/STAT, and the PI3K/Akt pathway along with the subsequent effects on cell division and steroidogenesis indicates that these growth factors are centrally located to alter cell fate during proliferation and survival. In this review, we will explore the function of GH and IGF in regulating normal ovarian and testicular physiology, while also investigating the effects on cell signal transduction pathways with subsequent changes in cell proliferation and steroidogenesis. The aim is to clarify the role of GH in human fertility from a molecular and biochemical point of view.

Dppa2/4 promotes zygotic genome activation by binding to GC-rich region in signaling pathways

“…Folate also plays a critical role in the synthesis of S-adenosylmethionine (SAM) (Kim, 2000), which deficiency results decreased level of SAM, thereby resulting in abnormal methylation of Igf2 and other genes (Fig 5). Among them, we found that the knockout of Dppa2 and 4 down-regulates the expression level of Igf2 gene (Fig 5 and Appendix Fig S3D), which further causes the abnormality of signaling pathways regulated by Igf2, such as MAPK, PI3K-Akt and Ras signaling pathways (Aksamitiene et al , 2012; Ipsa et al , 2019). These pathways are also regulated by Dppa2/4, in agreement with the fact that the complex interactions between these signaling pathways are mainly involved in development and the alteration of cell fate.…”

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

“…The PI3K/Akt pathway plays a crucial role in the regulation of GC growth and apoptosis during follicular development [18][19][20]. When PI3K is phosphorylated and activated by growth factors, it can phosphorylate Akt protein [29]. p-Akt phosphorylates FOXO1 and inhibits its nuclear localization and transcription activity [23].…”

“…GH both directly connects with the cell-surface GH receptor and indirectly improves the expression of insulin-like growth factor (IGF-1); IGF-1 then binds its cell-surface receptor [29]. Consequently, the insulin receptor substrate is activated and PI3K produces PI-3,4,5-trisphosphate (PIP3) [29]. PIP3 phosphorylates Akt and p-Akt downregulates FOXO1, inhibits Bax expression and increases Bcl-2 expression [37].…”

Regulatory Potential of Long Non-Coding RNAs (lncRNAs) in Boar Spermatozoa with Good and Poor Freezability

“…According to the study of Ran et al [ 11 ], sperm transcripts related to apoptotic-related signaling pathways, such as JAK–STAT and the P13K–Akt cascade, might have a regulatory role in apoptosis during cryopreservation. The GHR is a member of the cytokine receptor superfamily, and GH has multiple specific effects on the male reproductive physiology, including steroidogenesis and spermatogenesis [ 44 ]. Notably, the testis-specific cells are potential targets for direct and indirect actions of THRB , a receptor for the thyroid hormone (TH) which regulates the proliferation and differentiation of the Sertoli cells and Leydig cells during testicular development [ 45 , 70 ].…”