toxic effects of methoxychlor on the episodic prolactin secretory pattern: possible mediated effects of nitric oxide production

Abstract

Background

This work addresses the issue of whether methoxychlor (MTX) exposure may modify the ultradian secretion of prolactin through changes in the synthesis of nitric oxide (NO) induced by N^ω-nitro-L-arginine methyl ester (L-NAME) in the hypothalamic-pituitary axis. Associated changes in dopamine (DA) content in the anterior (AH), mediobasal (MBH) and posterior hypothalamus (PH) and median eminence (ME) were evaluated.

Methods

Two groups of animals (MTX and MTX+L-NAME treated) received subcutaneous (sc) injections of MTX at a dose of 25 mg/kg/day for one month. The other two groups of animals (control and L-NAME treated) received sc vehicle injections (0.5 mL/day of sesame oil), during the same period of time to be used as controls. Forty hours before the day of the experiment, animals were anaesthetized with intrapritoneal injections of 2.5% tribromoethanol in saline and atrial cannulas were implanted through the external jugular vein. Plasma was continuously extracted in Hamilton syringes coupled to a peristaltic bomb in tubes containing phosphate-gelatine buffer (to increase viscosity). The plasma was obtained by decantation and kept every 7 minutes for the measurement of plasma prolactin levels through a specific radioimmnunoassay and DA concentration by high-pressure liquid chromatography (HPLC).

Results

Prolactin release in animals from all experimental groups analyzed was episodic. Mean plasma prolactin levels during the bleeding period, and the absolute pulse amplitude were increased after MTX or N^ω-nitro-L-arginine methyl ester (L-NAME) administration. However MTX and L-NAME did not modify any other parameter studied with the exception of relative pulse amplitude in MTX treated rats. L-NAME administration to rats treated with the pesticide reduced mean plasma prolactin levels and the absolute amplitude of prolactin peaks. Peak duration, frequency and relative amplitude of prolactin peaks were not changed in the group of rats treated with MTX plus L-NAME as compared to either control or MTX treated rats. Whereas MTX decreased DA content in the ME and increased it in the AH, its content did not change in the MBH or PH, as compared to the values found in controls. Also, L-NAME administration decreased DA content in the ME as compared to controls. However, L- NAME administration to MTX exposed rats, markedly increased DA content in the ME as compared to either MTX treated or control rats. L-NAME administration increased DA content in the AH as compared to the values found in non-treated rats. However L-NAME administration to MTX exposed rats did not modify DA content as compared to either MTX treated or control rats. L-NAME administration did not modify DA content at the MBH nor in saline treated nor in MTX treated rats. However, the values of DA in the MBH in MTX plus L-NAME treated animals were statistically decreased as compared to L-NAME treated rats. In the PH, L-NAME administration increased DA content as compared to the values found in non-treated animals. L-NAME administration to MTX exposed rats also increased DA content as compared to either MTX treated or control rats.

Conclusion

The results suggest the existence of an interaction between MTX and L-NAME in the modulation of the ultradian prolactin secretion at the pituitary levels. The possibility of an indirect effect mediated by changes in DA content at the ME requires further examination.