messengers). The exact cascade of biochemical reactions that follows Gprotein activation depends on the type of second-messenger system activated. One of the most ubiquitous second messengers, cyclic adenosine
monophosphate (cAMP), is produced by the enzyme adenylate cyclase (Fig.
6.3). Activated G-protein regulates adenylate cyclase to increase the levels
of cAMP. cAMP activates cellular enzymes called protein kinases that are
localized both in the membrane and in the cytoplasm. Activated protein
kinases in the membrane phosphorylate structural proteins embedded in
the membrane and modify the ultimate physiological function of the cell
by changing the permeability of membrane ion channels. Protein kinases in
the cytoplasm, when in an activated state, bind to the response elements of
some genes and alter protein synthesis. In addition to cAMP, other secondmessenger systems, such as the inositol phospholipid (IP)-calcium system,
are also activated by G-proteins and change calcium ion concentrations
in the cytoplasm. In the IP-calcium system, an active G-protein activates
enzyme phospholipase C (PLC) in the cell membrane. PLC has important
effects on intracellular concentrations of Ca
2+
, which plays an important
role in determining the efficacy of neurotransmission in neurons. PLC first
converts phosphatidyl inositol phosphate (PIP 2 ) into two components,
diacylglycerol (DAG) in the membrane and inositol triphosphate (IP 3 )
released into the cytoplasm. Cytoplasmic IP 3 modifies the intracellular concentration of Ca
2+ by releasing intracellular stores of calcium, and DAG
brings in extracellular Ca
2+ by changing the permeability of Ca
2+ channels
via protein kinase C (PKC). Free intracellular Ca
2+
, in turn, increases
soluble PKC to phosphorylate additional proteins. Peptide hormones therefore can trigger diverse cascades of intracellular events by utilizing different kinds of second-messenger systems.
2.3. Systemic and Organismal Effects of Hormones
The primary (intracellular) biochemical responses induced by steroid and
peptide hormones in target cells described above can lead to secondary and
tertiary biochemical responses in those cells and ultimately result in more
global changes at systemic and organismal levels. Hormone-induced protein
synthesis may lead to modifications in enzymatic activity, rates at which
other proteins are synthesized, cell morphology, and overall number of
hormone receptors and ion channels. Hormone-induced changes in membrane permeability in neurons or neurosecretory cells can modify the
release of neurotransmitters, neuromodulators, and/or hormones.These secondary changes influence the biological function of nontarget cells via intercellular communication. As we will see later, the steepest challenge the field
of behavioral endocrinology faces is interpreting hormone-induced
secondary and tertiary physiological and structural changes in terms of
behavior.
282
A. Yamaguchi and D.B. Kelley
monophosphate (cAMP), is produced by the enzyme adenylate cyclase (Fig.
6.3). Activated G-protein regulates adenylate cyclase to increase the levels
of cAMP. cAMP activates cellular enzymes called protein kinases that are
localized both in the membrane and in the cytoplasm. Activated protein
kinases in the membrane phosphorylate structural proteins embedded in
the membrane and modify the ultimate physiological function of the cell
by changing the permeability of membrane ion channels. Protein kinases in
the cytoplasm, when in an activated state, bind to the response elements of
some genes and alter protein synthesis. In addition to cAMP, other secondmessenger systems, such as the inositol phospholipid (IP)-calcium system,
are also activated by G-proteins and change calcium ion concentrations
in the cytoplasm. In the IP-calcium system, an active G-protein activates
enzyme phospholipase C (PLC) in the cell membrane. PLC has important
effects on intracellular concentrations of Ca
2+
, which plays an important
role in determining the efficacy of neurotransmission in neurons. PLC first
converts phosphatidyl inositol phosphate (PIP 2 ) into two components,
diacylglycerol (DAG) in the membrane and inositol triphosphate (IP 3 )
released into the cytoplasm. Cytoplasmic IP 3 modifies the intracellular concentration of Ca
2+ by releasing intracellular stores of calcium, and DAG
brings in extracellular Ca
2+ by changing the permeability of Ca
2+ channels
via protein kinase C (PKC). Free intracellular Ca
2+
, in turn, increases
soluble PKC to phosphorylate additional proteins. Peptide hormones therefore can trigger diverse cascades of intracellular events by utilizing different kinds of second-messenger systems.
2.3. Systemic and Organismal Effects of Hormones
The primary (intracellular) biochemical responses induced by steroid and
peptide hormones in target cells described above can lead to secondary and
tertiary biochemical responses in those cells and ultimately result in more
global changes at systemic and organismal levels. Hormone-induced protein
synthesis may lead to modifications in enzymatic activity, rates at which
other proteins are synthesized, cell morphology, and overall number of
hormone receptors and ion channels. Hormone-induced changes in membrane permeability in neurons or neurosecretory cells can modify the
release of neurotransmitters, neuromodulators, and/or hormones.These secondary changes influence the biological function of nontarget cells via intercellular communication. As we will see later, the steepest challenge the field
of behavioral endocrinology faces is interpreting hormone-induced
secondary and tertiary physiological and structural changes in terms of
behavior.
282
A. Yamaguchi and D.B. Kelley