The secretion of hypothalamic, pituitary, and target tissue hormones is under tight regulatory control by a series of feedback and feed- forward loops. This complexity can be demonstrated using the growth hormone (GH) regulatory system as an example. The stimulatory substance growth hormone releasing hormone (GHRH) and the inhibitory substance somatostatin (SS) both products of the hypothalamus, control pituitary GH secretion. Somatostatin is also called growth hormone-inhibiting hormone (GHIH). Under the influence of GHRH, growth hormone is released into the systemic circulation, causing the target tissue to secrete insulin-like growth factor-1, IGF-1. Growth hormone also has other more direct metabolic effects; it is both hyperglycemic and lipolytic. The principal source of systemic IGF-1 is the liver, although most other tissues secrete and contribute to systemic IGF-1. Liver IGF-1 is considered to be the principal regulator of tissue growth. In particular, the IGF-1 secreted by the liver is believed to synchronize growth throughout the body, resulting in a homeostatic balance of tissue size and mass. IGF-1 secreted by peripheral tissues is generally considered to be autocrine or paracrine in its biological action.
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.
Another explanation could be reduced 5'-deiodinase tissue activity, resulting in decreased T3 production from T4 and reduced breakdown of rT3. The decreased production of T3 during early and late starvation has been explained as either a diminished activity of the enzyme (deiodinase) itself or a deficiency of cytosolic cofactors, such as NADPH or glutathione. Specific deiodinative enzymes, 3 of which have been identified, affect deiodination of iodothyronines. Type 1 deiodinase is present in the liver, kidney, and thyroid and affects both 5 and 5' deiodination of T3. Type 2 deiodinase is present in the brain, pituitary, and brown adipose tissue and is active only in 5' deiodination. Type 3 deiodinase is found particularly in the brain, skin, and placenta, and it deiodinates iodothyronines at the 5 locations.