Steroidal hormones

Hopeite Hopper cars Hops Horderns Horehound Hormocel Hormonal steroids... 

C. Djerassi, Excerpta Medica International Congress Series No. 132, Proceedings of the Second International Congress on Hormonal Steroids, 1966. 

R. Wiechert, Proc. First Intern. Congr. Hormonal Steroids, 2, 77 (1962). 

This method was described by L. Nedelec (Centre de Recherches Roussel UCLAF, Romainville, France) in a lecture at the Third International Congress on Hormonal Steroids, Hamburg, Germany, September 9-12, 1970. 

W. Schneider, D. Ayer and J. Huber, Abstracts of 2nd International Congress of Hormonal Steroids, Milan, Italy, 1966. 

P. A. Desaulles and B. Schar, Proc. Sec. Intern. Cong. Hormonal Steroids (Excerpta Medica Intern. Congress Series No. 132), 1967, p. 541. 

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. 

Historically, the 1950s represented an important time in the control of human fertility. It was during that decade that the first combined oral contraceptives were developed. Shortly after the discovery that the exogenous administration of hormones such as progesterone successfully blocked ovulation, the use of hormonal steroids quickly became the most popular method of contraception worldwide. Specifically, combined oral contraceptives represent the most commonly used reversible form of contraception today and it is estimated that nearly 100 million women worldwide take oral contraceptives.1 Further, in the United States, it is estimated that at some time during their lives, more than 80% of women born since 1945 have used oral... 

Understanding of the intracellular localization of steroid receptors has gone through a number of phases, beginning with the view that receptors translocated from cytoplasm to nucleus in the presence of hormone. Indeed, with the exception of thyroid hormone receptors, which are exclusively nuclear in location, cell fractionation studies have revealed that in the absence of hormone, steroid receptors are extracted in the soluble or cytosolic fraction. However, when steroid is present in the cell, many occupied receptors are retained by purified cell nuclei. Histological procedures, such as immunocytochemistry, have confirmed the largely nuclear localization of occupied receptors, but... 

Fig. 1.1. General mechanism of action of steroid hormones. Steroid hormones cross through the plasmatic membrane without apparent difficulty favored by gradient. Some, which can be considered prohormones, are metabolized and transformed into more active products. This is the case with testosterone, which becomes dihydrotestosterone (DHT) in the target tissues of androgens, through the 5-alfa-reductase enzyme. The hormone binds to the receptor, a soluble protein of the cellular cytosol that, in the absence of hormone, is found associated with other proteins (hsp90 and others) that maintain the receptor in an inactive state. The hormone-receptor bond causes the other proteins to separate and a homodimer to be formed. The homodimer is the activated form of the receptor since it is capable of recognizing the genes that depend on that steroid hormone as well as of activating its expression, which leads to the synthesis of specific proteins...

Adrenal cortex Glucocorticoids Mineralocorticoids Sex hormones Steroids... 

Industrialized and developed countries with effective regulatory systems— less than 1% of total market mainly lifestyle drugs such as hormones, steroids, and antihistamines... 

Ecdysone is the steroid hormone of the arthropods. It can be regarded as an early form of the steroid hormones. Steroid hormones with signaling functions also occur in plants. 

The third class of lipids is steroids. Included in this category of lipids are cholesterol, bile salts, and sex hormones. Steroid structures contain fused rings consisting of three six-carbon rings and a five-carbon ring ... 

While the clinical use of MS/MS of hormonal steroids is new, metabolite analysis by gas chromatography (GC)-mass spectrometry (MS) has been available for 40 years, since few immunoassays were developed for urinary analytes. Profile analysis is a very powerful technique and it must be recognized that with few exceptions, all disorders of steroid synthesis and metabolism first had their metabolome defined... 

Positive-ion MS is used in the majority of published works and is preferable for most hormonal steroids, with the possible exception of aldosterone. Estrogens and steroid conjugates have greater sensitivity in negative-ion mode. 

Griffiths et al. [23] studied the ESI MS of sterols, and while they are not hormonal steroids, similar derivatization methods can be used. He converts 3/5-hydroxy-A5 sterols to - -4-ene sterols using cholesterol oxidase and follows this by preparation of Girard P hydrazones. This increases the sensitivity by 1000 in ESI. This technique would also be applicable to pregnenolone, dehydroepiandrosterone (DHEA) and similar A5 steroids, which can also be oxidized by cholesterol oxidase. 

Kushnir et al. [44, 45] also measured 17-hydroxyprogesterone within a profile of four adrenal steroids (detailed in Hormonal Steroid Profiles below). They utilized an oxime derivative to improve ESI sensitivity and carried out analyses on an ABI 4000 instrument. Rauh and co-workers [70] published a method for 17-hydroxyprogesterone with ancillary measurement of androstenedione and testosterone. The mass spectrometer was an ABI 4000 instrument with an APCI source, operated in positive-ion mode and with on-line cartridge sample extraction and column switching. The MRM transitions were as used by other workers (Table 5.3.1)... 

Corticosterone is a component of the steroid profile (see Hormonal Steroid Profiles , below) developed by Guo et al. [25]. The analysis uses positive APPI and a d8 corticosterone internal standard. MRM was conducted with the m/z 347—>121, and 355—>125 transitions, respectively. The lower detection limit (LOD) was 2 pg/ml. Quest Diagnostics offer MS/MS analysis of this steroid commercially and have published normative values, as listed in Table 5.3.1. Marwah et al. [56] have published a method for the quantitation of corticosterone in rat plasma using electrospray MS. MS/MS methods for deoxycorticosterone (DOC) have not been published. 

CAH caused by 11/Thydroxylase deficiency is diagnosed by finding elevated 11-de-oxycortisol. This steroid is included in the profiles of Guo et al. [24,25] and Kushnir et al. [44] described below in Hormonal Steroid Profiles . Guo et al. monitored the transitions m/z 347—>97 for the analyte and 349—>97 for the dideutero internal standard. Kushnir et al., utilizing the oxime derivative monitored transitions 371—>24 and 112 for the analyte and 379—>124 and 112 for the dideutero standard. Quest diagnostics offer this MS/MS method and provide most of the quantitative values listed in Table 5.3.1. 

These steroids are components of the profile of Kushnir et al. [44, 45] and are discussed below in Hormonal Steroid Profiles . They were analyzed as the oxime derivatives by ESI on an API 4000 instrument. The MRM transitions for pregnenolone oxime were 332—>86 and 300, and for the d4 internal standard 336—>90 and 334. Transitions for 17HP were 348—>330 and 312, and for the d3 internal standard 351—>333 and 315. The publication gives quantitative data for Tanner stage 1-5 male and female children and for several age groups up to 52 years. 

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