doi:10.1016/S0006-291X(02)00603-4 Woollard, Kevin J, and Frederic Geissmann
They collected data on intracellular phosphorylated protein species and expression levels, constructed a Boolean network model, and conducted simulations to analyze cellular senescence signal transduction
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The ligand-receptor interaction triggers recruitment and autophosphorylation of JAK2 (Janus kinase) at the cytoplasmic domain of the GHR, and the GHR/JAK2 complex subsequently phosphorylates STAT (signal transducer and activator of transcription) molecules (particularly STAT5a, 5b, 1, and 3), which translocate to the nucleus and modify gene transcription leading to significant effects on cell proliferation (Figure 2) ( It is not obvious which hormone or system is more important, as ovarian function can be influenced by systemic GH and IGF, local GH, GH-induced local IGF, and/or GH-independent IGF ( The systemic IGF system is made up of IGF-1 and IGF-2 ( Analogous to GH, IGF-1 stimulates proliferation and differentiation of granulosa cells and theca cells ( in vitro study performed by Magalhes-Padilha et al., demonstrated a higher growth rate of IGF-1 stimulated caprine preantral follicles and they stipulated that it was most likely due to cellular proliferation, as it was demonstrated that IGF-1 enhanced nuclear maturation of granulosa cells in preantral follicles ( Animal studies using genetic knock-outs also demonstrated a more direct role for IGFs over GH in reproduction
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