Box 205

Functional Considerations: Cholesterol

Cholesterol is the basic precursor of corticosteroid hormones. It is synthesized from cholesterol esters stored in lipid droplets within the cytoplasm of adrenal cortical cells. Steroid hormones are synthesized from cholesterol esters by removal of part of the side chain and modifications at specific sites on the remainder of the molecule. The enzymes catalyzing these modifications are located in different zones of the cortex as well as in different cytoplasmic sites within the cells. A precursor molecule may move from the sER to a mitochondrion and back again several times before the definitive molecular structure of a given corticosteroid is obtained.

Cholesterol esters removed from cytoplasmic lipid droplets and used in steroid hormone synthesis are quickly replenished from the cholesterol esters contained within low-density lipoproteins (LDLs) carried in the bloodstream. These esters are the primary source of the cholesterol used in corticosteroid synthesis. In addition, a small portion of cholesterol used for hormone synthesis comes from de novo synthesis of cholesterol by the adrenal cortical cells. Under conditions of short-term or prolonged ACTH stimulation, the lipid stores in adrenal cortical cells are recruited for corticosteroid synthesis.

The zona reticularis is also under feedback control of the CRH-ACTH system and atrophies after hypophysectomy. Exogenous ACTH maintains the structure and function of the zona reticularis after hypophysectomy.

Fetal Adrenal Gland

The fetal adrenal gland consists of an outer narrow permanent cortex and an inner thick fetal cortex or fetal zone

Once fully established, the fetal adrenal gland is unusual in terms of its organization and its large size relative to other developing organs. The gland arises from mesodermal cells located between the root of the mesentery and the developing gonad zone (see Fig. 20.17a). The mesodermal cells penetrate the underlying mesenchyme and give rise to a large eosinophilic cell mass that will become the functional fetal cortex or zone (see Fig. 20.17b). Later, a second wave of cells proliferates from the mesenchyme and surrounds the primary cell mass (see Fig. 20.17c). By the fourth fetal month, the adrenal gland reaches its maximum mass in terms of body weight and is only slightly smaller than the adjacent kidney. At term, the adrenal glands are equivalent in size and weight to those of the adult and produce 100 to 200 rng of steroid compounds per day, about twice that of the adult adrenals.

The histologic appearance of the fetal adrenal gland is superficially similar to that of the adult adrenal gland. During late fetal life, most of the gland consists of cords of large eosinophilic cells that constitute approximately 80% of its mass. This portion of the gland, referred to as the fetal cortex (zone), arises from the initial mesodermal cell migration. The remainder of the gland is composed of the peripheral layer of small cells with scanty cytoplasm. This portion, referred to as the permanent cortex, arises from the secondary mesodermal cell migration. The narrow permanent cortex, when fully established in the embryo, ap pears similar to the adult zona glomerulosa. The cells are arranged in arched groups that extend into short cords. They, in turn, become continuous with the cords of the underlying fetal zone (Fig. 20.23). In H&E preparations, the cytoplasm of the cells in the permanent cortex exhibits some basophilia; in combination with the closely packed nuclei, this gives this part of the gland a blue appearance, in contrast to the eosinophilic staining of the fetal zone.

With the TEM, the cells of the permanent cortex exhibit small mitochondria with shelf-like cristae, abundant ribo-somes, and small Golgi profiles. The cells of the fetal zone, in contrast, are considerably larger and are arranged in irregular cords of varying width. With the TEM, these cells exhibit spherical mitochondria with tubular cristae, small lipid droplets, an extensive sER that accounts for the eosinophilia of the cytoplasm, and multiple Golgi profiles. Collectively, these features are characteristic of steroid-se-creting cells.

The fetal adrenal lacks a definitive medulla. Chromaffin cells are present but are scattered among the cells of the fetal zone and are difficult to recognize in H&E preparations. The chromaffin cells originate from the neural crest (see Fig. 20.17a) and invade the fetal zone at the time of its formation (see Fig. 20.17b). They remain in this location in small, scattered cell clusters during fetal life (see Fig. 20.17c).

The blood supply to both the permanent cortex and the fetal zone is through sinusoidal capillaries that course between the cords and join to form larger venous channels in the center of the gland. Unlike the postnatal adrenal, arterioles are absent in the parenchyma of the fetal adrenal gland.

Functionally, the fetal adrenal gland is under the control of the CRH-ACTH feedback system through the fetal pituitary. It interacts with the placenta to function as a steroid-secreting organ because it lacks certain enzymes necessary for steroid synthesis that are present in the placenta. Similarly, the placenta lacks certain en chapter 20 i Endocrine Organs 669

chapter 20 i Endocrine Organs 669

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