Figure 1 summarizes the six tropic peptide hormones that stimulate the biosynthesis of six essential steroid hormones. The top row identifies the six peptide/proteins that are the stimulatory hormones (chemical messengers). The second row lists six separate endrocrine glands each with a specific receptor for the partner tropic hormone (top row). Each endocrine gland is the site of production of a different specific steroid hormone. It is important to appreciate that the production of each steroid hormone is dependent upon the stimulation of its cells of origin by a specific tropic (stimulatory) peptide hormone. For example, ACTH that is secrected by the pituitary moves through the circulatory system to the zona fasciculata region of the adrenal cortex where it binds to its partner receptor. This then results in the stimulation of the metabolism of cholesterol to produce the steroid hormone cortisol, a glucocorticoid that is released into the circulatory system. The cortisol steroid hormone then delivers its chemical message by travel through the circulatory system to its several target organs, which include the liver, muscle, and adispose tissue.
Fig1. Relationships between stimulatory peptides or protein hormones and the endocrine glands that are the site of production of six steroid hormones. For each of the six classes of steroid hormones, the specific stimulatory or tropic hormone is indicated (see top row) as well as specification of the organ or cell upon which it acts (see second row), and finally (see bottom row) the newly synthesized steroid hormone. Thus for the tropic hormone ACTH the newly synthesized steroid is a glucocorticoid (cortisol). The tropic luteinizing hormone (LH) has different assignments in males (production of testosterone) and females (production of progesterone). Follicle stimulating hormone (FSH) also has different assignments in females (production of estradiol) and in males where it acts upon the Sertoli cells in the seminiferous tubules not to increase the production of a steroid hormone but to increase the synthesis of the sperm proteins, androgen-binding protein, and inhibin, a peptide hormone.
Figure 2 summarizes both the anatomical sites and major steps of biosynthesis from cholesterol to the final target steroid for each of the six classes of steroid hormones. These include the adrenal cortex (green panel), which is anatomically divided into the outer layer zona glomerulosa (aldosterone), the middle layer zona fasciculata (the glucocorticoids corticosterone and cortisol), and an inner layer zona reticularis (the androgen testosterone). The peach-colored panel (Figure 2) focuses on the ovary, which is anatomically divided into the corpus luteum (progesterone) and the theca and granulosa cells (estradiol). The yellow panel (Figure 2) focuses on the testes’ Leydig cells (testosterone). The blue panel (Figure 2) summarizes anatomically the five key steps for conversion of cholesterol into 7-dehydrocholesterol and then vitamin D3 (in the skin) followed by 25-hydroxylation (in the liver) and followed by pro duction of the steroid hormone 1α,25(OH)2D3 and the metabolite 24,25(OH)2D3 (both in the kidney).
Fig2. Pathways of biosynthesis of the principal families of human steroid hormones. Each color panel represents a different anatomical location for the biosynthesis of the designated steroid family. They include the adrenal cortex panel (in light green) for its zona glomerulosa (aldosterone), zona fasciculata (cortisol and corticosterone), and the zona reticularis (testosterone). Each of the “zona” regions are separated by a dashed line. The sex steroid hormones are shown in the light peach panel for the female ovarian corpus luteum (progesterone), the female ovarian theca and granulosa cells (estradiol); and in yellow the male testes Leydig cells (testosterone). The bottom blue panel summarizes the biosynthetic steps in the skin, liver, and kidney for conversion of cholesterol into vitamin D3 and then into its steroid hormone, 1α,25(OH)2-vitamin D3. [Modified with permission from W. L. Miller and R. J. Auchus, The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr. Rev. 32, 81–151 (2011).]
The bile acids, which are the seventh important structural class of mammalian steroids, are principally synthesized in the liver and they function as detergents in vivo to facilitate digestion and absorption of lipids. Also, some orphan nuclear receptors, e.g., the farse noid X receptor (FRX) and the LXRα receptor, were found to specifically bind cholic and chenodeoxycholic acids and to regulate selected gene transcription.
