4.2 The male sexual dimorphism-related GnRH signaling pathway
GnRH is secreted from the hypothalamus and plays a key role in the
control of vertebrate reproductive functions by binding to its specific
membrane receptor, GnRHR, triggering the synthesis and release of
pituitary gonadotropins, including follicle-stimulating hormone (FSH),
LH, and CG, to induce gonads that produce sex steroids for gametogenesis
(Fernald and White, 1999; Okubo and Nagahama, 2008). In the
hypothalamus-pituitary-gonadal axis, the GnRH signaling cascade control
process is essential for maintaining gonadotropin synthesis and release.
It plays an important role in developing secondary sex characteristics
(Bosch et al., 2021).
Almost all gene families in the GnRH signaling pathway have been
identified in the male O. bidens genome, and multiple expanded
genes are present in the node steps of this pathway. First, GnRHR
transmits its signal to activate phospholipase C by coupling channel
proteins, such as guanine nucleotide-binding protein subunits Gs and
Gq/11. Subsequently, the subtypes of G proteins and their receptors
represent the components of a highly versatile signal transduction
system, centrally involved in hormone release and actions (Wettschureck
and Offermanns, 2005). Receptor-G protein coupling requires
diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) after
ligand-dependent receptor activation, and the G protein occasionally
occurs in a cell-specific manner (Krsmanovic et al., 2003; Ruf et al.,
2003). The intracellular PKC pathway supports the primary mechanism for
hormone release and action activated via DAG by releasing intracellular
calcium and activating the calcium signaling pathway stimulated via IP3
(Du et al., 2015).
In the present study, out of 138 genes involved in the GnRH signaling
pathway in male O. bidens , 78 showed at least a 3-fold increase
in essential nodes regulating gonadotropin hormone secretion by
pituitary gonadotrope cells. The top three gene families were CaMKII,
p38MAPK, and cytosolic phospholipase A2 (PLA2). It has been reported
that the Ca2+ increase is fast and transient upon
binding of most hormone receptors and that CaMKII, which is a ubiquitous
serine/threonine protein kinase, is enriched in the IP3 pathway and
activated by Ca2+ signals and calmodulin (CaM) to
phosphorylate diverse substrates involved in metabolism and hormone
release (Illario et al., 2003). LH synthesis and secretion are
influenced by cytokines transported to the pituitary gland through the
blood and act on endocrine pituitary cells. The p38MAPK and PLA2 genes
are enriched in the PKC pathway, and when p38 MAPK is inhibited by a
small-molecule inhibitor, the LH expression decrease at mRNA levels
(Jian et al., 2021). PLA2 is a large family of calcium-dependent
phospholipases with the ability to directly interact with G-proteins and
kinases (Song et al., 1999), resulting in short sequestration in
activating regulated LH secretion (Melamed et al., 2012). LH production
induces growth hormone (GH) and regulates GH secretion and synthesis
(Chen et al., 2018a; Fontaine et al., 2020; Fung et al., 2017). Our
results indicate that the expanded genes in the GnRH signaling pathway
play an important role in sexual dimorphism in male O. bidens .