Table 1.

Intraovarian Paracrine Hormones Act Through RTKs, RSKs, GPCRs, Guanylyl Cyclase Receptor NPRB, and Integrins to Regulate Preantral Follicle Growth^a

Ligands	Receptors
IGF-1, KGF, VEGF, FGF2, FGF10	RTKs
Activins, BMP6, AMH	RSKs (types I and II)
PACAP, VIP	GPCRs
CNP	Guanylyl cyclase (NPRB)
CCN2/CTGF	Integrins

Abbreviations: CTGF, connective tissue growth factor.

^aDiverse paracrine growth factors are secreted by granulosa cells; they act through several distinct intracellular signaling pathways to promote follicle development. IGF-1, KGF, VEGF, FGF2, and FGF10 act through their respective RTKs in granulosa cells to regulate follicle development. In contrast, activins, AMH, and BMP6 synthesized by granulosa cells act though type I and type II RSKs in granulosa cells to regulate follicle development. Also, both PACAP and VIP produced by granulosa cells increase cAMP production by granulosa cells to regulate follicular functions. CNP secreted by granulosa cells binds to the guanylyl cyclase NPRB to increase cGMP production and promote follicle development. In contrast, CCN2/CTGF, produced by granulosa cells in response to Hippo signaling disruption, interacts with membrane-bound integrins in granulosa cells to promote follicle growth.