Sex steroid hormones exert biphasic effects on cytosolic magnesium ions incerebral vascular smooth muscle cells: Possible relationships to migraine frequency in premenstrual syndromes and stroke incidence

Clinically, it is known that: (1) magnesium (Mg) supplementation relieves p remenstrual problems (e.g., migraine, bloating and edema) occurring in the late luteal phase of the menstrual cycle; and (2) migraine syndromes, parti cularly in women, are associated with deficits in brain and serum ionized M g levels. We investigated whether concentrations of sex steroid hormones, f ound in the serum during the menstrual cycle of women, are associated with changes in the levels of cytosolic free magnesium ions ([Mg2+](i)) in singl e cultured canine cerebral vascular smooth muscle cells. The resting level of [Mg2+](i) in these cells was 645 +/- 89 muM before exposure to sex stero id hormones. Exposure of these vascular cells to a low concentration of est rogen (10 pg/ml) failed to interfere with the levels of [Mg2+](i). However, exposure to estrogen, at concentrations ranging from 40 to 200 pg/ml, indu ced significant loss of [Mg2+](i) in a concentration-dependent manner. At a concentration of 200 pg/ml estrogen, the level of [Mg2+](i) decreased simi lar to 30% in comparison with controls. Progesterone produced biphasic effe cts on the levels of [Mg2+](i) depending an its concentration. Exposure of the cultured cells to a low concentration of progesterone (0.5 ng/ml) resul ted in an increased level of [Mg2+](i) (from 690 +/- 50 muM to 753 +/- 56 m uM, p < 0.05). However, when these cells were exposed to higher concentrati ons of progesterone (i.e., from 5.0 to 20 ng/ml), the cellular levels of [M g2+](i) were decreased significantly. The higher the estrogen or progestero ne concentration, the lower the levels of [Mg2+](i). In contrast, testoster one, a male hormone, didn't produce any significant alteration in [Mg2+](i) levels in these cerebral vascular smooth muscle cells. These data indicate that low, physiological concentrations of female sex hormones, estrogen an d progesterone, help cerebral vascular smooth cells sustain normal concentr ations of [Mg2+](i), which are beneficial to vascular function, whereas hig h levels of estrogen and progesterone deplete, significantly, [Mg2+](i) in cerebral vascular smooth muscle cells, possibly resulting in cerebrovasospa sms and reduced cerebral blood flows related to premenstrual syndromes, mig raine and stroke risk. Our findings could provide new insight into the mech anism whereby migraine occurs frequently in the late luteal phase in the pr emenstrual syndrome. In addition, our results demonstrate that female sex s teroids but not testosterone tin physiologic concentrations) can exert dire ct effects on [Mg2+](i) in cerebral vascular cells. (C) 2001 Elsevier Scien ce Inc.