Epigenetics of Reproduction in Animals - Building the Most Complex Structure on Earth - page 108

Hormones are secreted by endocrine glands, but growth factors are induced by
hormones. So, for example, Wnt is induced by progesterone during the morphogen-
esis of the mammary gland; inhibin, a member of the TGF-beta family of growth
factors, is induced by the pituitary FSH; expression of the Igf- 1 (insulin growth
factor-1) gene is induced by the GH and by the neurohormone VIP, and so on.
It is now common knowledge that in eumetazoans, the secretion of all hormones
from the target endocrine glands (thyroid, pancereas, adrenals, ovaries, and testicles)
is induced by secretion of specific “stimulating” hormones in the pituitary; hence,
the designation of the pituitary as the “master gland.” But soon the master gland
turned out to be subordinate to another part of the brain, called the hypothalamus.
Secretion of each of the pituitary hormones is induced by a specific “releasing” hor-
mone produced by the hypothalamus.
Genetic marks, DNA methylation, and histone modifications also seem to be reg-
ulated by extracellular signal cascades. DNA methylation is the function of methyl-
transferases, but these enzymes are activated by hormones such as glucocorticoids
and E2. In turn, these hormones are respectively regulated by the pituitary ACTH and
FSH and, farther upstream, by the hypothalamic neurohormones CRH and GnRH.
Histone modification (e.g., acetylation, deacetylation, and methylation) are
regulated via neuroendocrine cascades. So, for example, acetylation of histones
in the ovarian granulosa cells induces the expression of FSH-responsive genes.
Sometimes the nervous system is directly involved in histone modification. Such is
the case with expression of AChR in the NMJ; axon terminals of the motor neuron
release in the junction agrin, which, by activating a signal transduction pathway,
enables the recruitment of acetylating enzymes, modification of the histone, and
the exposure of genes for transcription. (For an expanded discussion of this issue,
see the section “Neural Origin of Epigenetic Information for Epigenetic Structures”
earlier in this chapter.)
By connecting the intracellular signal transduction pathways with the neuroen-
docrine cascades, we may see the expression of particular genes as the result of a
general signal cascade that starts with brain signals. This seems to be a common
mechanism of gene expression based on epigenetic information (chemical signals)
released in the brain as an output of the processing of internal and external stimuli.
This epigenetic information flows through neuroendocrine signal cascades, which
via intracellular signal transduction pathways send the epigenetic message to one or
a number of specific genes. In a generalized form, the neuroendocrine signal cascade
for the expression of a gene is presented in Figure 5.16.
This neuroendocrine model, however, cannot explain the fact that these circulat-
ing chemicals induce gene expression in certain cells and regions of the animal body,
while repressing it in other cells and regions. A neural mechanism of spatial restric-
tion of gene expression in animal bodies will be described in Chapter 3.
The neural control of gene expression is a surprising revelation in modern biol-
ogy. A further discussion on the nature of this control is beyond the scope of this
topic, but interested readers can find extensive information on this topic in my topic
Epigenetic Principles of Evolution ( Cabej, 2012 ), especially in Chapter 2.