Page 70 - Clinical Small Animal Internal Medicine

38 Section 2 Endocrine Disease

its production by the pituitary and indirectly by altering enteral cells of the stomach, is a potent GH secreta-
VetBooks.ir GnRH receptor sensitivity. Activin, a protein produced gogue. Other factors known to directly or indirectly
influence GH secretion include nutritional states, stress,
by the ovaries, and dopamine are known stimulators
of FSH release. Endogenous opioids have an inhibitory
is stimulated by alpha‐adrenergic agonists and inhib-
influence on gonadotropin production through altera- sex steroids, and exercise. For example, GH secretion
tion of GnRH secretion. ited by beta‐adrenergic agonists and hyperglycemia.
Estradiol modulates GH levels indirectly via inhibitory
Somatomammotropic Hormones effects on SS.
Growth hormone and prolactin (PRL) are grouped
together as the somatomammotropic hormones. Their Prolactin Prolactin is involved in the regulation of lacta-
amino acid sequences are similar, which may account for tion and reproduction. PRL works together with sex ster-
some common functions. oids to stimulate mammary gland development and
regulate milk production during lactation. Although
Growth Hormone As the name suggests, GH regulates PRL is secreted in the male, its physiologic role is not yet
growth and development. In young animals, it stimulates fully elucidated.
growth of connective tissue, long bones, muscles, and Prolactin is a single‐chain polypeptide containing
endocrine glands. GH is a metabolic counterregulatory three disulfide bridges. There is significant sequence var-
hormone, which opposes the actions of insulin and raises iation between species. PRL secretion is pulsatile, and
glucose by stimulating hepatic gluconeogenesis and stimulated by the hypothalamic hormones prolactin‐
impairing glucose uptake in muscle. GH stimulates lipol- releasing hormone (PRLH) and TRH. PRL is also released
ysis in adipose tissue, which results in increased circulat- in response to the neural stimulation of suckling during
ing free fatty acids, and has an anabolic effect on protein lactation. The definitive identity of PRLH is not yet
synthesis. GH stimulates production of insulin‐like known, but vasoactive intestinal peptide (VIP) has been
growth factor 1 (IGF‐1) by hepatocytes. IGF‐1 is a pri- suggested. PRL release is inhibited by dopamine, which is
mary mediator of the effects of GH. also referred to as prolactin‐inhibiting hormone. In the
Growth hormone is a single‐chain polypeptide con- regulation of PRL release, the inhibitory component is
taining two disulfide bridges. The sequence is highly known to predominate over the stimulatory component.
conserved among species; the sequences of canine and Upon binding to its receptors in lactotropic cells,
feline GH differ by only one amino acid, while those of dopamine inhibits PRL release. PRL, in turn, acts in a
canine and porcine GH are identical. Receptors for GH short feedback loop by circulating and binding to PRL
have been identified throughout the body, but are found receptors on dopaminergic neurons in the hypothala-
in the highest concentrations in skeletal muscle, liver, mus. PRL release is also stimulated by oxytocin and angi-
adipose tissue, heart, kidneys, lungs, and cartilage. This otensin II, and inhibited by gamma‐aminobutyric acid
diffuse distribution in part explains GH’s diverse effects. (GABA). Unlike other hypophyseal hormones, PRL is
GH receptors are known to have altered sensitivity to not subject to typical feedback inhibition by target tissue
various secretagogues throughout life, which aids in hormone products. Instead, its release is solely regulated
preferential growth and development in young, and spe- through hypothalamic input and the suckling reflex.
cialized metabolic function in adults.
Growth hormone secretion is pulsatile, and results Proopiomelanocortin‐Derived Peptides
from the complex interactions between growth hor- Proopiomelanocortin is a large prohormone which
mone‐releasing hormone (GHRH), SS, and peripheral encodes numerous secretory products (Figure 5.2). It is
factors (both neural and hormonal). GH release is pri- synthesized by corticotropic cells of the anterior pitui-
marily a reflection of the delivery and binding of hypo- tary and melanotropic cells of the IL. Proteolytic enzymes
thalamic GHRH to pituitary somatotropic cells. SS is a hydrolyze POMC into ACTH and beta‐lipotropin (beta‐
known inhibitor of GH secretion, thus high GHRH and LPH). These products are then further cleaved into
low SS levels result in GH release. SS is a more potent alpha‐MSH, which stimulates melanin production by
inhibitor of GH release than of TSH release. epithelial cells and leads to darkening of skin, beta‐
Insulin‐like growth factor 1 is secreted in response to endorphin (an endogenous opioid), and other related
GH, but is also responsive to systemic alterations in peptides. The function of many of these peptides is not
energy balance and nutrition. Low levels of IGF‐1 stimu- yet fully understood and remains under investigation.
late GH release. As GH and IGF‐1 levels rise, they Proopiomelanocortin synthesis is under direct neu-
feed back on the hypothalamus to decrease GHRH and ral control by the hypothalamus primarily through
increase SS secretion, which results in reduced produc- inhibitory dopaminergic innervation. Thus, dopamine
tion of GH. Ghrelin, an endogenous ligand produced by exerts tonic inhibition of POMC release under normal