Pregnenolone secretion

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

The apocrine glands in the axilla can secrete enormous amounts of steroids such as dihydrotestosterone and pregnenolone (Brooksbank, 1970). Three single steroid compounds have also been tested on T-shirts. Surprisingly, both sexes attributed androstenol to females. Two other synthetic compounds were attributed to one or the other sex, depending on concentration, and one was perceived as very negative. Androstenol and the two synthetic compounds have very low olfactory thresholds for humans. 

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

FUNCTION Stimulates pregnenolone production and cortisol secretion in adrenal cortex. 

As shown in Figure 5.3, pregnenolone (I) is oxidised to progesterone (II) and thence converted via 17a-hydroxyprogesterone (III) into testosterone (V). Testosterone is the most active of the naturally occurring androgens [9, 10]. Androstenedione (VI) and dehydroepiandrosterone (DHA) (IV) form less potent but quantitatively more significant secretion products. 

In the 3 jS-hydroxysteroid dehydrogenase deficiency, the conversion of pregnenolone or pregnenolone derivatives to progesterone is blocked. Such a block precludes the formation of glucocortico- and mineralo-corticosteroids. Consequently, most individuals with complete dehydrogenase deficiency die in early infancy. A small number of cases have been reported in which the enzymic block is incomplete, and enough cortisol is secreted to secure survival. 

The development of the various adrenal enzymes in the fetal adrenal may also be of considerable significance in interpreting the lack of activity observed after birth. jS-Hydroxysteroid dehydrogenase is low in fetal liver thus, the pathway prevails (pregnenolone— dehydroepiandrosterone), and cortisol synthesis is low. The relatively large adrenals found in utero may result from compensatory hyperplasia in response to low cortisol secretion. In early embryonic life, 21- and 11-hydroxylase activities are low, but they increase with the age of the fetus. 

Sulfotransferases from tumoral and normal adrenals were shown capable of conjugating many steroids in vitro pregnenolone, 17-hydroxypreg-nenolone, corticosterone, deoxycorticosterone, testosterone, as well as the adrenal androgens were readily sulfated (Gual et al., 1962 Cohn et al., 1963 Lebeau and Baulieu, 1963 Adams, 1964 Bostrom et al., 1964 Killinger and Solomon, 1965). Indirect evidence, obtained from isotopic dilution studies, pointed to a possible secretion of pregnenolone sulfate... 

Pearlman, 1957 Vande Wide el al., 1960) >out one half of this progesterone is produced by the placenta itself. Consequently, the prc esterone produced by the placental compartment is obtmned principally (1) from pregnenolone which is synthesized via acetate or cholesterol or by hydrolysis of pregnenolone-3/S-suIfate secreted by the fetus and (2) by oxidation of 20a-dihydroprogesterone which comes principally from the fetal compartment. 

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