Steroid metabolic disturbances in Prader‐Willi syndrome

Abstract

We have studied steroid sulfate conjugates in serum samples from 17 children with Prader-Willi syndrome (PWS) by extraction, enzymatic hydrolysis and chromatography of the hydrolysed, free steroids. The chromatograms in patients with PWS can be divided into 2 classes. Ten (4 with the deletion on chromosome 15 and 6 without) of 17 had a normal pattern with dehydroepiandrosterone (DHEA) as the only steroid detected. However, 7 out of 17 (3 with the deletion and 4 without) had a very different pattern. The chromatogram derived from these hydrolysates had 5 major peaks. One of these was DHEA; a second peak was tentatively identified as 16 alpha-hydroxy-DHEA on the basis of column retention time and immunoreactivity. The remaining 3, more polar, compounds have not yet been identified. The presence of unusual steroid sulfoconjugates in serum may correlate with other features of PWS and may be the basis for dividing PWS into two separate disease states: a) PWS-1 associated with DHEA-S as the only sulfo-conjugate and b) PWS-2 associated with unusual sulfo-conjugates. One interesting possibility is that these sulfo-conjugates may have a hormonal function, even though no function has yet been recognized for DHEA-S. Then, PWS may be the common clinical manifestation of a variety of different defects in the sulfo-conjugate metabolic pathway.

Whole genome microarray analysis of gene expression in Prader–Willi syndrome

“…STAR plays a key role in the acute regulation of steroid hormone synthesis by enhancing the conversion of cholesterol into pregnenolone. This observation is supported by steroid metabolite disturbances previously reported in PWS [Chasalow et al, 1987]. Specifically, Chasalow et al 1987 reported that PWS subjects secreted large amounts of sulfo‐conjugates, including dehydroepiandrosterone (DHEA) and mono‐ and dihydroxypregnenolone.…”

“…This observation is supported by steroid metabolite disturbances previously reported in PWS [Chasalow et al, 1987]. Specifically, Chasalow et al 1987 reported that PWS subjects secreted large amounts of sulfo‐conjugates, including dehydroepiandrosterone (DHEA) and mono‐ and dihydroxypregnenolone. In addition, pregnane steroids can potently and specifically enhance GABA A receptor function acting as remote endocrine messengers [Lambert et al, 2003; Belelli and Lambert, 2005].…”

Increased Adrenal Androgen Levels in Patients with Prader-Willi Syndrome Are Associated with Insulin, IGF-I, and Leptin, but Not with Measures of Obesity

“…To date, growth hormone (GH) insufficiency and hypogonadism are well described, and the gonadal development at puberty is typically delayed or incomplete. Surprisingly, in this context, premature adrenarche may be observed in children affected by PWS [11, 12, 13, 14, 15], although the insulin [16]and IGF-I [17]levels are below the normal average due to insufficient GH secretion [18]. The issue of accelerated adrenal development against a background of hypothalamic-pituitary insufficiency in PWS has not yet been explained.…”

Dexamethasone Suppressible Hypergonadotropism in an Adolescent Patient with Prader-Willi Syndrome.

“…It is probable that the observed increase in DHEA-S may be similar to increased DHEA-S in pubarche or precocious puberty. On the other hand, Chasalow et al(1987) suggested that Prader-Willi syndrome may have the common clinical manifestations of a variety of different defects in the sulfoconjugate metabolic pathway. Adrenal suppression by dex.…”