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Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ERα and ERβ) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles of ERα and ERβ, mouse endometrial stromal cells and ovarian granulosa cells were treated with ligands specific for individual estrogen receptors. In endometrial stromal cells, propyl-pyrazole-triol (PPT; ERα-selective agonist) increased Igf1 mRNA expression, which was suppressed by methyl-piperidino-pyrazole (MPP, ERα-selective antagonist), while diarylpropionitrile (DPN, ERβ-potency selective agonist) increased Igf1 mRNA expression, which was inhibited by MPP but not by 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-3-yl]phenol (PHTPP; ERβ antagonist). PHTPP enhanced the DPN-induced increase in Igf1 mRNA expression. In ovarian granulosa cells, E2 and DPN decreased Igf1 mRNA expression, whereas PPT did not affect Igf1 mRNA levels. In these cells, PHTPP inhibited the DPN-induced decrease in Igf1 mRNA expression. These results suggest that ERα facilitates Igf1 transcription, whereas ERβ appears to inhibit Igf1 gene transcription in mouse endometrial stromal cells and ovarian granulosa cells.

In the present study, the possibility of an interaction between prescription drugs and over-the-counter (OTC) drugs was investigated by monitoring plasma drug concentrations in rats. When a levodopa preparation (Madopar®) indicated for patients with Parkinson's disease was orally administered with Saclon®, an OTC drug for upset stomach, the AUC and Cmax for levodopa were significantly lowered and Tmax was significantly prolonged. These results indicate that there may be an interaction between a levodopa preparation and Saclon® when administered together, which leads to a reduction in the bioavailability of levodopa. Similar results were obtained when the levodopa preparation and the main ingredient of Saclon®, a copper chlorophyllin salt, were concomitantly administered. Taken together, our results indicate that the copper chlorophyllin salt in Saclon® may interact with levodopa preparations. The possibility of such an interaction should therefore be kept in mind during levodopa therapy for patients with Parkinson's disease.

Transforming growth factor-α (TGFα) is thought to be involved in the regulation of endometrial cells. We investigated Tgfa mRNA expression, and the effects of TGFα on DNA-synthesis and gene expression of insulin-like growth factor 1 (IGF1), IGF binding protein-3 (IGFBP3) and IGF1 receptor in the mouse endometrial cells, because IGF1 is involved in estrogen-induced growth of endometrial cells. We also investigated the role of TGFα on matrix metalloproteinase (MMP) expression, as MMPs are involved both in tissue remodeling during cell proliferation and in enhancement of IGF1 signaling through the degradation of IGFBP3. Tgfa mRNA expression was detected in endometrial luminal and glandular epithelial cells, and stromal cells. Tgfa mRNA signals did not appear to change in endometrial luminal epithelial cells, but signals in glandular epithelial cells were higher at diestrus 1, 2 and proestrus, and the number of stromal cells showing strong signals appeared to increase at diestrus 1 and 2. Endometrial epithelial and stromal cells were treated with estradiol-17β (E2) or progesterone (P4). E2 or P4 stimulated Tgfa mRNA expression in stromal cells. TGFα stimulated DNA synthesis in endometrial epithelial and stromal cells, while E2 and P4 stimulated DNA synthesis in stromal cells. In stromal cells, TGFα, at as low as 1 ng/ml, decreased Igfbp3 and Mmp9 mRNA levels, while high dose (10 ng/ml) of TGFα decreased Igf1 mRNA level and increased Mmp3 mRNA level. These results imply that TGFα stimulates proliferation of endometrial stromal cells through multiple mechanisms, including its regulation of Igfbp3 and Mmp3 transcription.

This study aimed to examine the effects of banana juice on levodopa bioavailability in rats. When a levodopa preparation (EC-Doparl tablets) was orally administered with banana juice made by mixing with a fresh banana and water, there were significant decreases in C(max) (17.4+/-2.5 vs. 8.6+/-3.1 microg/ml; alpha=0.05) and AUC (1882.8+/-49.2 vs. 933.5+/-286.6 microg.min/ml; alpha=0.05) for levodopa. On the other hand, administration of the levodopa preparation with a commercial beverage containing 10% banana juice resulted in no significant change in C(max) or AUC. These results indicate that concomitant intake of levodopa preparations with banana juice, but not with a commercial banana beverage, may cause a drug-food interaction reducing levodopa bioavailability, and we should pay attention to such interactions during levodopa therapy for patients with Parkinson's disease.