Platelets

Platelets are released into the blood stream as fragments of cells in the bone marrow called megakaryocytes. Each megakaryocyte contains a nucleus. Therefore, hormones can cause activation or repression of genes in the nuclei of megakaryocytes. However, once in the blood steam, although platelets still respond to sex hormones like estrogen and testosterone, regulation of genes is not possible as these cell fragments do not contain nuclei. Once released into the blood, platelets live about 10 days. New platelets are continuously produced to replace those that die. At any one time, then, the circulating population of platelets contains platelets which were formed and released under different hormonal influences in the bone marrow. For example, a women who has been post-menopausal for about 5 years will have a population of circulating platelets that developed under the lack of estrogen. As she begins estrogen-treatment, the population of circulating platelets will respond to the hormones in the blood. However, new platelets that are developing in the bone marrow will be influenced by changes in gene transcription. Over time as old platelets die and new ones are formed, the circulating population will take on new characteristics such that estrogen "primed" platelets will gradually replace those that developed under estrogen deplete conditions. Until a new steady state is reached, circulating platelets will represent a mixed population, i.e. those that developed under estrogen-deplete and estrogen-replete conditions. Experiments in our laboratory are aimed at understanding how changes in platelet characteristics contribute to risk for development of blood clots in the legs, heart attack and stroke.

Effects of Ovarian Hormones on Platelet-Derived Factors

Hormones, for example 17β-estradiol, through stimulation of estrogen receptors alpha and beta (ER α and β) alter transcription of genes (mRNA) in megakaryocytes. Production of proteins may be altered as shown in this example where estrogen (17 β-estradiol) stimulates production of platelet-derived growth factor (PDGF) and matrix metalloproteinase-2 (MMP-2) but not transforming growth factor (TGFβ). These factors when released during platelet activation at the site of vascular injury will initiate cell division and migration of cells to repair the "vascular wound" and cause blood clots.