Progesterone cortisol from

It has been shown that the fetal adrenal can convert progesterone and pregnenolone into cortisol in substantial yield (Sections 4.2.1 and 4.2.2), and, notably, Solomon (S25), after perfusion of fetuses with proges-terone-4- C, has isolated radioactive corticosterone and cortisol from the... 

Progesterone, cortisol, cortisone, aldosterone and related compounds have hormone activity in animals (E 3.1). Progesterone regulates the metabolic activity of the gonads. It is synthesized mainly in the corpus luteum and the placenta. Cortisol, cortisone, and aldosterone influence carbohydrate and mineral metabolism. They are formed in the adrenal cortex (corticosteroids), but also in the gonads and the placenta. All compounds mentioned are used in medicine (F 2) and are produced by the pharmaceutical industry, e.g., from steroid saponins (D 6.4.2) or steroid alkaloids (D 6.4.3). 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

Congenital defects in the biosynthesis of steroid hormones can lead to severe developmental disturbances, in the adrenogenital syndrome (AGS), which is relatively common, there is usually a defect in 21-hydroxylase, which is needed for synthesis of cortisol and aldosterone from progesterone. Reduced synthesis of this hormone leads to increased formation of testosterone, resulting in masculin-ization of female fetuses. With early diagnosis, this condition can be avoided by providing the mother with hormone treatment before birth. 

The mammary gland consists of the external nipple and the system of ducts from the alveoli to the skin surface. The alveoli do not fully develop until a female experiences pregnancy and lactation. Cortisol, insulin and placental lactogen contribute to alveolar development, but estrogen and progesterone are most important. The cells that line the alveoli synthesize milk, and they are surrounded by a layer of myoepithelial cells that eject the milk. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

Hormones detected in milk include some from the peptide and steroid classes but none of the amino hormones. Prolactin, a protein of 199 amino acid residues, is normally present in a concentration of about 50 /tg/liter, and the hexapeptide gonadotropin-releasing hormone of the hypothalmus at about 1.5 g/liter. Steroid hormones from the adrenal cortex include the glucocorticoids cortisol and corticosterone, totaling 0.2-0.6 /tg/liter. Those from the ovary—progesterone, estrone, and estradiol—have concentrations of 10-30, 30, and 175 /ig/liter, respectively. Hormones in milk have been reviewed by Koldovsky (1980) and Pope and Swinburne (1980). The prolactin in milk is biologically active (Gala et al. 1980). 

Severe consequences can occur from defective syn- thesis of a steroid hormone, as is the case in several metabolic diseases. Patients who have 21-hydroxylase deficiency are unable to convert progesterone to aldosterone and cortisol. Instead the progesterone is directed to an excess production of testosterone. In the female, this results in masculinization and hirsutism (growth of hair). In the male, premature masculinization occurs. If the disease is diagnosed before the first birthday, the patient can be treated with the missing steroid hormones, which in turn suppress the synthesis of excess progesterone and, as a consequence, testosterone via feedback mechanisms. 

The step-by-step synthesis of the steroid hormones pregnenolone and progesterone from cholesterol (C27) was presented in chapter 20 (see fig 20.22). Note that pregneno-lone (C2i) and progesterone (table 20.4) (C2 ) are intermediates in the biosynthesis of all of the major adrenal steroids, including cortisol (C2i), corticosterone (C21), and aldosterone (C21). The same two compounds are intermediates in the synthesis of the gonadal steroid hormones, testosterone (C,9) and 17/3-estradiol (CI8). Because the synthesis of all these hormones follows a common pathway, a defect in the activity or amount of an enzyme along that pathway can lead to both a deficiency in the hormones beyond the affected step and an excess of the hormones, or metabolites, prior to that step. 

Small quantities of progesterone, testosterone, and estradiol are also produced by the adrenal gland. However, they play a minor role compared to the testicular and ovarian hormones. Progesterone, which is the precursor of cortisol, aldosterone, testosterone, and estradiol, is synthesized from 5-pregnenolone by 3-P-ol-dehydrogenase. Deficiency of this enzyme results in cortisol and aldosterone deficiencies. Such patients require replacement therapy with both glucocorticoids and mineralocorticoids. 

Cholesterol is an extremely important biological molecule that modulates the fluidity of animal cell membranes and is the precursor of steroid hormones (such as progesterone, testosterone, oestradiol and cortisol) and bile acids. Cholesterol is either derived from the diet or synthesised de novo. Regardless of the source, cholesterol is transported through the circulation in lipoprotein particles, as are cholesterol esters, the cellular storage form of cholesterol. The amount of cholesterol synthesised daily in the liver of a normal person is usually double that obtained from dietary sources. Other sites of cholesterol synthesis include the intestine, and the degree of production is highly responsive to cellular levels of cholesterol. Over 1.2 g of cholesterol is lost in the faeces daily in the form of free sterol or as bile acids. 

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