Melatonin-Induced Increase in Cytoplasmic Estrogen Receptor Activity in Hamster Uteri*

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Abstract
The pineal gland hormone, melatonin, was shown to influence the growth and metabolism of uterine tissue in the Syrian hamster. Because the uterus is an estrogen-responsive target tissue, the effect of melatonin on the unoccupied estrogen receptor (ER) activity of immature hamster uteri in vivo and in vitro was studied. A single s.c. injection of 2.5 .mu.g melatonin increased the ER activity of uterine cytosol (Rc) 30% within 60 min [from 147.4 .+-. 14.1 (SE), to 191.8 .+-. 18.5 fmol/mg protein]. Scatchard analysis showed the induced population of receptor to be homogeneous and of high affinity, with an equilibrium Kd = 0.08 nM similar to that for uteri for vehicle-treated animals. The induction of Rc by melatonin persisted for 90 min, but Rc returned to control levels by 2 h after injection. Scatchard analysis of unoccupied nuclear receptor showed no significant differences either in the quantity of receptor (vehicle = 379.7 .+-. 46.7, melatonin = 396.9 .+-. 76.7 fmol/mg protein) or in the Kd (vehicle = 0.75 nM, melatonin = 0.60 nM) between these 2 groups. In vitro incubation of fresh whole uteri for 60 min in media containing 10-5 M melatonin increased Rc by 83% (from 41.3 .+-. 10.7 to 75.4 .+-. 11.0 fmol/mg protein), supporting a direct effect of melatonin on uterine tissue. The Rc induced by melatonin both in vivo and in vitro was sensitive to the degree of homogenization used in preparation of the cytosol. While conservative homogenization (two 10 s bursts with an intermittent 40-s cooling period) of uteri from melatonin-treated animals was associated with a significant increase in Rc, homogenization for 60 s without intermittent cooling showed a significant decrease (from 251.1 .+-. 17.4 to 182.7 .+-. 5.8 fmol/mg protein) as compared with uteri from vehicle-treated animals. Whole organ analysis of uteri from animals injected with melatonin followed by [3H]estradiol, in which no homogenization was used, demonstrated a 26% increase in Rc specific binding, confirming induction as the primary response to melatonin. These findings demonstrate the ability of melatonin to modulate ER activity in hamster uteri, and may help explain the effects of melatonin on uterine growth and metabolism.