The estrogens are a family of hormones synthesized in a variety of tissues. 17β-Estradiol is the primary estrogen of ovarian origin. In some species, estrone, synthesized in numerous tis sues, is more abundant. In pregnancy, relatively more estriol is produced, and this comes from the placenta. The general pathway and the subcellular localization of the enzymes involved in the early steps of estradiol synthesis are the same as those involved in androgen biosynthesis. Features unique to the ovary are illustrated in Figure 1.

Fig1. Biosynthesis of estrogens.(Reproduced with permission from Barrett KE, Barman SM, Brooks HL, et al: Ganong’s Review of Medical Physiology, 26th ed. New York, NY: McGraw Hill; 2019.)

Estrogens are formed by the aromatization of androgens in a complex process that involves three hydroxylation steps, each of which requires O2 and NADPH. The aromatase enzyme complexis thought to include a P450 monooxygenase. Estradiol is formed if the substrate of this enzyme complex is testosterone, whereas estrone results from the aromatization of androstenedione.

The cellular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone to other steroid hormones (Figure 2).

Fig2. Biosynthesis of progesterone in the corpus luteum.

 Significant amounts of estrogens are produced by the peripheral aromatization of androgens. In human males, the peripheral aromatization of testosterone to estradiol (E2 ) accounts for 80% of the production of the latter. In females, adrenal androgens are important substrates since as much as 50% of the E2 produced during pregnancy comes from the aromatization of androgens. Finally, conversion of androstenedione to estrone is the major source of estrogens in postmenopausal women. Aromatase activity is present in adipose cells and also in liver, skin, and other tissues. Increased activity of this enzyme may contribute to the “estrogenization” that characterizes such diseases as cirrhosis of the liver, hyperthyroidism, aging, and obesity. Aromatase inhibitors show promise as therapeutic agents in breast cancer and possibly in other female reproductive tract malignancies.

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مواضيع ذات صلة

Cholesterol Side Chain Cleavage Enzyme (p450scc)

Steroidogenic Acute Regulatory Protein (StAR)

Cytochrome P450 Steroid Hydroxylases

Major Protein Components of Muscle Fibers

The Major Components of Cartilage are Type II Collagen & Certain Proteoglycans

Bone is Affected by many Metabolic & Genetic Disorders

The Assembly of Membranes is Complex

Transport Vesicle Formation and Function Involves SNAREs & Other Factors

Misfolded Proteins Undergo Endoplasmic Reticulum Associated Degradation

Proteoglycans & Glycosaminoglycans

The ER Functions as The Quality Control Compartment of The Cell

Proteins Follow Several Routes to be Inserted Into or Attached to The Membranes of The Endoplasmic Reticulum