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SECTION III
Central & Peripheral Neurophysiology
Hypophysiotropic hormones function as neurotransmit-
ters in other parts of the brain, the retina, and the autonomic
nervous system (see Chapter 7). In addition, somatostatin is
found in the pancreatic islets (see Chapter 21), GRH is
secreted by pancreatic tumors, and somatostatin and TRH are
found in the gastrointestinal tract (see Chapter 26).
Receptors for most of the hypophysiotropic hormones are
serpentine and coupled to G proteins. There are two human
CRH receptors: hCRH-RI, and hCRHRII. The latter differs
from the former in having a 29-amino-acid insert in its first
cytoplasmic loop. The physiologic role of hCRH-RII is unset-
tled, though it is found in many parts of the brain. In addition,
a
CRH-binding protein
in the peripheral circulation inacti-
vates CRH. It is also found in the cytoplasm of corticotropes
in the anterior pituitary, and in this location it might play a
role in receptor internalization. However, the exact physio-
logic role of this protein is unknown. Other hypophysiotropic
hormones do not have known binding proteins.
SIGNIFICANCE &
CLINICAL IMPLICATIONS
Research delineating the multiple neuroendocrine regulatory
functions of the hypothalamus is important because it helps
explain how endocrine secretion is made appropriate to the
demands of a changing environment. The nervous system re-
ceives information about changes in the internal and external
environment from the sense organs. It brings about adjust-
ments to these changes through effector mechanisms that in-
clude not only somatic movement but also changes in the rate
at which hormones are secreted.
The manifestations of hypothalamic disease are neurologic
defects, endocrine changes, and metabolic abnormalities such
as hyperphagia and hyperthermia. The relative frequencies of
the signs and symptoms of hypothalamic disease in one large
series of cases are shown in Table 18–2. The possibility of
hypothalamic pathology should be kept in mind in evaluating
all patients with pituitary dysfunction, especially those with
isolated deficiencies of single pituitary tropic hormones.
A condition of considerable interest in this context is
Kall-
mann syndrome,
the combination of hypogonadism due to low
levels of circulating gonadotropins
(hypogonadotropic hypo-
gonadism)
with partial or complete loss of the sense of smell
(
hyposmia
or
anosmia
). Embryologically, GnRH neurons
develop in the nose and migrate up the olfactory nerves and
then through the brain to the hypothalamus. If this migration is
prevented by congenital abnormalities in the olfactory path-
ways, the GnRH neurons do not reach the hypothalamus and
pubertal maturation of the gonads fails to occur. The syndrome
is most common in men, and the cause in many cases is muta-
tion of the
KALIG1
gene, a gene on the X chromosome that
codes for what is apparently an adhesion molecule necessary for
normal development of the olfactory nerve on which the GnRH
neurons migrate into the brain. However, the condition also
occurs in women and can be due to other genetic abnormalities.
TEMPERATURE REGULATION
In the body, heat is produced by muscular exercise, assimilation
of food, and all the vital processes that contribute to the basal
metabolic rate (see Chapter 27). It is lost from the body by radi-
ation, conduction, and vaporization of water in the respiratory
passages and on the skin. Small amounts of heat are also re-
moved in the urine and feces. The balance between heat produc-
tion and heat loss determines the body temperature. Because the
speed of chemical reactions varies with the temperature and be-
cause the enzyme systems of the body have narrow temperature
ranges in which their function is optimal, normal body function
depends on a relatively constant body temperature.
Invertebrates generally cannot adjust their body temperatures
and so are at the mercy of the environment. In vertebrates,
mechanisms for maintaining body temperature by adjusting heat
production and heat loss have evolved. In reptiles, amphibians,
and fish, the adjusting mechanisms are relatively rudimentary,
and these species are called “cold-blooded”
(poikilothermic)
because their body temperature fluctuates over a considerableTABLE 18–2
Symptoms and signs in 60 autopsied pa-
tients with hypothalamic disease.Symptoms and Signs Percentage of Cases
Endocrine and metabolic findings
Precocious puberty 40
Hypogonadism 32
Diabetes insipidus 35
Obesity 25
Abnormalities of temperature regulation 22
Emaciation 18
Bulimia 8
Anorexia 7
Neurologic findings
Eye signs 78
Pyramidal and sensory deficits 75
Headache 65
Extrapyramidal signs 62
Vomiting 40
Psychic disturbances, rage attacks, etc 35
Somnolence 30
Convulsions 15
Data from Bauer HG: Endocrine and other clinical manifestations of hypothalamic
disease. J Clin Endocrinol 1954;14:13. See also Kahana L, et al: Endocrine manifesta-
tions of intracranial extrasellar lesions. J Clin Endocrinol 1962;22:304.