The sex hormones

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. 

The male and female gonads, as well as the placenta of pregnant females and, to a lesser extent, the adrenal cortex, produce a range of steroid hormones which regulate the development and maintenance of reproductive and related functions. As such, these steroid sex hormones have found medical application in the treatment of various reproductive dysfunctions. 

While these steroids directly regulate sexual function, their synthesis and release are, in turn, controlled by gonadotropins — polypeptide hormones produced by the pituitary gland. The biology and medical applications of the gonadotropins are outlined in Chapter 8. Sex hormones produced naturally may be classified into one of three groups  

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As we have seen in this chapter steroids have a number of functions in human physiology Cholesterol is a component part of cell mem branes and is found in large amounts in the brain Derivatives of cholic acid assist the digestion of fats in the small intestine Cortisone and its derivatives are involved in maintaining the electrolyte balance in body fluids The sex hormones responsible for mascu line and feminine characteristics as well as numerous aspects of pregnancy from conception to birth are steroids... 

In addition to the sex hormones and corticosteroids, other steroid dmgs have substantial worldwide markets. For example, cytostatic hormones had worldwide sales of approximately 1.8 biUion in 1994. Included in these 1.8 biUion are several steroids or steroid-mimetics such as megestrol acetate and tamoxifen (282), respectively (262). 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

In humans, most steroids function as hormones, chemical messengers that are secreted by endocrine glands and carried through the bloodstream to target tissues. There are two main classes of steroid hormones the sex hormones, which control maturation, tissue growth, and reproduction, and the adrenocortical hormones, which regulate a variety of metabolic processes. 

The sex hormone estrone has been synthesized by a route that involves the following step. Identify the pericyclic reactions involved, and propose a mechanism. 

DHEA is an adrenal hormone that is a precursor to the sex hormones testosterone and estrogen, as well as other hormones. DHEA is reported to increase testosterone and decrease total body fat, and also to have anabolic and anti-aging effects. The... 

Nyman suggested that the minor sex difference may be ascribed to the influence of the sex hormones (Bll, S12) on Hp homeostasis (see Section 5.4.). 

In various tissues of the body, cholesterol is converted to several classes of steroid hormones. Let s begin with the sex hormones. 

Cells in the ovaries and testes produce the sex hormones oestrogen and progesterone in the female, and testosterone and androstenedione in the male (Chapter 19). 

To secrete a sex-hormone binding protein (SHBP) which binds the sex hormones in the blood to protect them from metabolism and hence inactivation. 

The control of the levels of the sex hormones, oestrogen, progesterone and testosterone, is achieved by feedback inhibition of the secretions of both the pituitary and hypo-... 

Examples are shown in Fig. 23.9. Stereochemistry is indicated by dotted lines (a-bonds, behind the plane) and solid lines (P-bonds, in front of the plane) of any substituents on the rings. The sex hormones are the molecules mainly responsible for differentiating the sexes. The difference between testosterone and progesterone is a hydroxy versus an acetyl group. The natural sex hormones are used to treat prostate cancer, to alleviate menopausal distress, and to correct menstrual disorders. Other common natural steroids are estradiol, cholesterol, and cortisone. Infamous... 

Steroids lipids that contain four fused carbon rings, three containing six carbons and one containing five carbons, include cholesterol and the sex hormones Sterols see Steroids... 

Of the various steroid hormones produced from cholesterol, the sex hormones are extremely important. The reproductive steroid hormones are divided into three classes ... 

The remaining steroid lipids constitute two main classes of steroid hormones sex hormones and adrenocortical hormones. The sex hormones include androgens (testosterone, androsterone), estrogens (estrone, estradiol), and progestins (progesterone). The adrenocortical hormones include mineralocorticoids (aldosterone) and glucocorticoids (hydrocortisone). 

The cortex of adrenal gland produces three types of hormones - the glucocorticoids, mineralocorticoids and the sex hormones. 

Steroids like cholesterol 335, cholic acid 336, or the sex hormone testosterone 337 play an important role in almost all living organisms. Therefore they are the... 

Cholesterol is a soft waxy substance that is a steroidal alcohol or sterol. It is the most abundant steroid in the human body and is a component of every cell. Cholesterol is essential to life and most animals and many plants contain this compound. Cholesterol biosynthesis occurs primarily in the liver, but it may be produced in other organs. A number of other substances are synthesized from cholesterol including vitamin D, steroid hormones (including the sex hormones), and bile salts. Cholesterol resides mainly in cell membranes. 

As well as the sex hormones already mentioned (see above), many other hormones seem to affect the metabolism of foreign compounds and therefore may have effects on toxicity. A number of pituitary hormones may directly, as well as indirectly, affect metabolism, for example, growth hormone, follicle-stimulating hormone, adrenocorticotrophic hormone, luteinizing hormone, and prolactin. Thus, hypophysectomy in male rats results in a general decrease in metabolism, but the effects of some of the individual hormones may depend on the sex of the animal and the particular enzyme or metabolic pathway. For example, adrenocorticotrophic hormone (ACTH) administration decreases oxidative metabolism in males but increases N-demethylation in female rats. Removal of the adrenal gland reduces metabolism, such as ethylmorphine demethylation and aniline 4-hydroxylation, and this can... 

Steroid hormones, derived from sterols, serve as powerful biological signals, such as the sex hormones. 

Steroids are a class of lipids that have in common a system of four linked carbon rings. Cholesterol, shown in Figure 13.14, is the most abundant steroid by far, and it serves as the starting material for the biosynthesis of most all other steroids, including the sex hormones estradiol and testosterone, also shown in Figure 13.14. Hormones are chemicals produced by one part of the body to influence other parts of the body. For example, estradiol, produced by the ovaries, and testosterone, produced by the testes, are responsible for the development of secondary sex characteristics in other parts of the body. Cholesterol is... 

The sex hormones estradiol and testosterone are steroids that the body produces from the most abundant steroid of all—cholesterol. 

Cholesterol is the starting material that the body uses to build many biologically important steroids, including the sex hormones. Although not mentioned in the text, you might be interested to know that cholesterol is also an important component of a cell s plasma membrane, which is strengthened by the various intermolecular forces exerted by the cholesterol. 

In the animal body three important groups of hormones are formed by the metabolism of cholesterol the progestins, the sex hormones, and the adrenal cortical hormones 249 Their synthesis occurs principally in mitochondria of the adrenal cortex and the gonads. Steroid hormone synthesis is regulated by hormones, such as corticotropin (ACTH), from the anterior pituitary250 (see Chapter 30) and is also dependent upon the recently discovered steroidogenic acute regulatory protein, which in some way promotes the movement of stored cholesterol into mitochondrial membranes.251 252 Some major pathways of... 

Cholesterol serves two important functions in the body. First, it is a minor component of cell membranes, where it helps to keep the membranes fluid. Second, it serves as the body s starting material for the synthesis of all other steroids, including the sex hormones. Although news reports sometimes make cholesterol sound dangerous, there would be no life without it. The human body obtains its cholesterol both by synthesis in the liver and by ingestion of food. Even on a strict no-cholesterol diet, an adult is able to synthesize approximately 800 mg per day. 

This chapter discusses the pharmacology of the steroid hormones that are produced by the adrenal cortex. The two primary types of adrenal steroids are the glucocorticoids and mineralocorticoids. Small amounts of other steroids such as the sex hormones (androgens, estrogens, and progestins) are also produced by the adrenal cortex. These steroids are discussed in Chapter 30. 

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