acetate as a substrate (Fig. 2.8), readily makes cholesterol, but it is possible that
some of this may also be accumulated from the blood. Cholesterol is subsequently
converted, via a series of intermediates, to progesterone, a pathway that seems to
be common to all endocrine glands that secrete steroid hormones. In the adrenal
cortex, progesterone may be converted to any of the three principal secretory products: cortisol, corticosterone or aldosterone, via two, and possibly three, principal
pathways. A series of hydroxylations take place involving the enzymes 17-hydroxylase and 21-hydroxylase, which are associated with the endoplasmic reticulum, an 11 .a-hydroxylase and 18-hydroxlase from the mitochondria. Progesterone, when hydroxylated at carbon 17, is converted to 17-hydroxyprogesterone,
which is successively further hydroxylated at carbons 21 and 11, to give cortisol.
This hormone can be oxidized, at carbon-Ll , to cortisone. If the progesterone
is alternatively hydroxylated at carbon-21, l l-deoxycorticosterone is produced,
which is then converted to corticosterone by hydroxylation at carbon-Ll , Corticosterone can be oxidized to l l-dehydrocorticosrerone or, by a series of changes
at the carbon-18, be converted to aldosterone. The formation of all aldosterone
secreted by the adrenal cortex cannot be accounted for by such a conversion, so
it seems likely that it is also made from progesterone in another way. A summary
of these reactions is given in Fig. 2.8 but it should be remembered that these processes have not been demonstrated in many species and the information available
is usually derived from mammals .
.a ) Physiology. The ph ysiological importance of the adrenals was first described
by THOMAS ADDISON in humans with diseased glands. These observations were
confirmed by extirpating the gland surgically in other mammals. The part of the
adrenal critical to life is the cortex, the chromaffin tissue of the medullary region
being dispensable. Acute removal of the adrenals in mammals is usually followed
by death in a few days, the associated physiological changes being comparable with
those seen in pathological situations. In mammals there are metabolic changes, such
as reduction in blood glucose and liver glycogen, a decrease in the level of plasma
sodium, and an increase in plasma potassium. Probably largely secondary to such
changes, there may be a reduction in extracellular fluid volume, a decrease in blood
pressure, reduced renal blood flow and glomerular filtration rate, and a low renal
clearance for urea and water. The effects on carbohydrate metabolism reflect reduced gluconeogenesis from protein and fat, as well as changes in peripheral util -
ization of metabolic substrates. The changes in plasma sodium and potassium levels
in mammals are mainly mediated by the kidney, which fails to conserve enough
sodium and secrete sufficient potassium.
While most mammals only survive for a few days following adrenalectomy
some animals, like rats, can occasionally live for extended periods due to the presence of accessory adrenocortical tissue . The American opossum, Didelphis virginiana, often survives for several months following removal of the adrenals but
this is not a marsupial character as one of its Australian relatives, the wallaby Setonix bracbyurus, dies in two to three days after such an operation (BuTTLE, KIRK,
and WARING, 1952). Survival of adrenalectomy can often be prolonged, though
not indefinitely, by providing the animals with saline solutions to drink, thus moderating the changes in bod y electrolyte levels.
74
some of this may also be accumulated from the blood. Cholesterol is subsequently
converted, via a series of intermediates, to progesterone, a pathway that seems to
be common to all endocrine glands that secrete steroid hormones. In the adrenal
cortex, progesterone may be converted to any of the three principal secretory products: cortisol, corticosterone or aldosterone, via two, and possibly three, principal
pathways. A series of hydroxylations take place involving the enzymes 17-hydroxylase and 21-hydroxylase, which are associated with the endoplasmic reticulum, an 11 .a-hydroxylase and 18-hydroxlase from the mitochondria. Progesterone, when hydroxylated at carbon 17, is converted to 17-hydroxyprogesterone,
which is successively further hydroxylated at carbons 21 and 11, to give cortisol.
This hormone can be oxidized, at carbon-Ll , to cortisone. If the progesterone
is alternatively hydroxylated at carbon-21, l l-deoxycorticosterone is produced,
which is then converted to corticosterone by hydroxylation at carbon-Ll , Corticosterone can be oxidized to l l-dehydrocorticosrerone or, by a series of changes
at the carbon-18, be converted to aldosterone. The formation of all aldosterone
secreted by the adrenal cortex cannot be accounted for by such a conversion, so
it seems likely that it is also made from progesterone in another way. A summary
of these reactions is given in Fig. 2.8 but it should be remembered that these processes have not been demonstrated in many species and the information available
is usually derived from mammals .
.a ) Physiology. The ph ysiological importance of the adrenals was first described
by THOMAS ADDISON in humans with diseased glands. These observations were
confirmed by extirpating the gland surgically in other mammals. The part of the
adrenal critical to life is the cortex, the chromaffin tissue of the medullary region
being dispensable. Acute removal of the adrenals in mammals is usually followed
by death in a few days, the associated physiological changes being comparable with
those seen in pathological situations. In mammals there are metabolic changes, such
as reduction in blood glucose and liver glycogen, a decrease in the level of plasma
sodium, and an increase in plasma potassium. Probably largely secondary to such
changes, there may be a reduction in extracellular fluid volume, a decrease in blood
pressure, reduced renal blood flow and glomerular filtration rate, and a low renal
clearance for urea and water. The effects on carbohydrate metabolism reflect reduced gluconeogenesis from protein and fat, as well as changes in peripheral util -
ization of metabolic substrates. The changes in plasma sodium and potassium levels
in mammals are mainly mediated by the kidney, which fails to conserve enough
sodium and secrete sufficient potassium.
While most mammals only survive for a few days following adrenalectomy
some animals, like rats, can occasionally live for extended periods due to the presence of accessory adrenocortical tissue . The American opossum, Didelphis virginiana, often survives for several months following removal of the adrenals but
this is not a marsupial character as one of its Australian relatives, the wallaby Setonix bracbyurus, dies in two to three days after such an operation (BuTTLE, KIRK,
and WARING, 1952). Survival of adrenalectomy can often be prolonged, though
not indefinitely, by providing the animals with saline solutions to drink, thus moderating the changes in bod y electrolyte levels.
74