Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Phosphocholine Steroid Conjugates: Are these Compounds the Mammalian Cardiotonic Steroids?

Version 1 : Received: 8 July 2020 / Approved: 10 July 2020 / Online: 10 July 2020 (09:55:05 CEST)

How to cite: Chasalow, F. Phosphocholine Steroid Conjugates: Are these Compounds the Mammalian Cardiotonic Steroids?. Preprints 2020, 2020070211 (doi: 10.20944/preprints202007.0211.v1). Chasalow, F. Phosphocholine Steroid Conjugates: Are these Compounds the Mammalian Cardiotonic Steroids?. Preprints 2020, 2020070211 (doi: 10.20944/preprints202007.0211.v1).

Abstract

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

Subject Areas

Ionotropin; Steroid phosphocholine esters; pre-eclampsia; endogenous ouabain; DLM; PTSD

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