Vitamin D: a steroid hormone with progesterone-like activity

G. Monastra, S. De Grazia, L. De Luca, S. Vittorio, V. Unfer

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. vunfer@gmail.com

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• Pharmacology

OBJECTIVE: This review is aimed at demonstrating the progesterone-like activity exerted by the active form of vitamin D, or calcitriol (1,25(OH)2D). To achieve this outcome, we compared the effects in vivo and in vitro exerted by progesterone and vitamin D, with a special focus on the female reproductive system and pregnancy.

MATERIALS AND METHODS: This is a literature review of the most important articles published in English on vitamin D as a hormone, mainly found by MEDLINE. Furthermore, a section of our review contains some unpublished data, concerning the analysis in silico of the similarities between the steric structure of progesterone and calcitriol, based on the availability of the experimental structures of progesterone and vitamin D3 receptors in complex with their physiological ligands in the RCSB Protein Data Bank.

RESULTS: Vitamin D was shown to exert many physiological activities during the very early stages of gestation in perfect synchrony with progesterone. Both the molecules mutually help and reinforce the activity exerted by each one. A little bit later than progesterone is released, vitamin D secretion rises, but only if pregnancy occurs. Calcitriol contributes to prepare the endometrium to be receptive. Moreover, it supports the implantation process and the course of pregnancy through different but similar pathways to those used by progesterone, giving rise to a significant synergy of action. It is increasingly evident that vitamin D gives an essential support from the luteal phase onwards.

CONCLUSIONS: Based on the evidence displayed in this review we may define appropriately vitamin D as a steroid hormone with progesterone-like activity.

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