Modulatory effect of estradiol and testosterone on the development of N-nitrosodiisopropanolamine induced thyroid tumors in female rats.

Both experimental and clinical research support the conclusion that thyroid tumors are sex dependent. Also, several studies have pointed out that the use of oral contraceptives is associated with a higher risk of thyroid tumor. Most of the existing reports suggest indirect effects of sex steroids on thyroid tumor growth in women. In this work, we present data to support the direct promoting effect of estradiol and testosterone on carcinogen-induced thyroid tumorigenesis. Thyroid tumors were induced in rats by a combination of N-nitrosodiisopropanolamine (DHPN) and phenobarbital (PB) treatment. Serum thyroid hormones, thyroid stimulating hormone (TSH), steroid hormones, thyroidal steroid concentration, androgen and estrogen receptors were quantified. Serum thyroid hormones and TSH suggested euthyroid status of the all experimental animals. Ovariectomy decreased the incidence of DHPN + PB induced thyroid tumor when compared with ovary intact rats and estradiol/testosterone supplementation increased the same. Thyroidal estradiol level and its nuclear receptors increased in the tumor tissue specifically. Testosterone supplementation to DHPN-treated ovariectomized rats specifically induced the development of malignant thyroid tumors. Addition of estradiol in vitro to thyrocytes induced a higher proliferation rate. Our data proves a direct promoting role of estrogen on carcinogen-induced thyroid tumor development.

Effect of lithium and sodium valproate ions on resting membrane potentials in neurons: an hypothesis.

In an attempt to understand the therapeutic effects of lithium and sodium valproate in stabilizing the moods in manic depressive illness, the well-known Goldman-Hodgkin-Katz (G-H-K) equation is modified to include a fourth ion, such as a lithium ion or a sodium ion. The modified G-H-K equation is used to calculate the resting membrane potential in neurons. These calculations show that the resting membrane potential is depolarized depending upon the relative concentration of the lithium ion and upon its relative permeability. These calculations suggest that the resting membrane potential may be hyperpolarized in bipolar patients before treatment, and that the lithium ion perhaps depolarizes the resting membrane potential back to the normal level. They further support the prevailing hypothesis that manic-depressive illness may be caused by the hyperpolarization of the resting membrane potential, which, in turn, may be caused by the changes in ionic conductance (permeability) of the membranes. Sodium ions in sodium valproate do not significantly affect the resting membrane potential since they do not significantly change in the serum.