Increased dietary fat consumption is associated with colon cancer development. The exact mechanism by which fat induces colon cancer is not clear, however, increased bile acid excretion in response to high-fat diet may promote colon carcinogenesis. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, and bile acids are endogenous ligands of FXR. FXR is highly expressed in the intestine and liver where FXR is essential for maintaining bile acid homeostasis. The role of FXR in intestine cancer development is not known. The current study evaluated the effects of FXR deficiency in mice on intestinal cell proliferation and cancer development. The results showed that FXR deficiency resulted in increased colon cell proliferation, which was accompanied by an up-

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Abstract.The effect of T3 on basal and LH mediated synthesis and secretion of testosterone and oestradiol by puberal rat Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 103) were cultured for 48 hours at 34 ° C in a medium containing a range of 5-400 ng/mL concentration of T3 or ovine LH after 24 hours initial culture at 37 °C. T3 increased testosterone and oestradiol secretions in a dose dependent manner which reached the saturation point with 50 ng dose. While the minimum effective dose of T3 (25 ng) potentiated the stimulatory effect of the minimum effective dose of LH (25 ng) on testosterone secretion, it suppressed the effect of the saturation dose of LH (100 ng). Fifty ng T3 quelled the stimulatory effect of either dose of LH. Both doses of T3 increased oestradiol secretion, irrespective of the dose of LH. Addition of androstenedione (500 ng/mL) to the culture medium enhanced 25 ng T3 induced testosterone and oestradiol secretions. While androstenedione potentiated the stimulatory effect of T3 (25 ng) on LH (25 ng) induced testosterone and oestradiol secretions, it reversed the inhibitory effect of 50 ng T3 on LH mediated testosterone secretion which was accompanied by a decrease in oestradiol secretion. Puromycin (35 pg/mL) suppressed the stimulatory effect of T3 on basal and LH mediated testosterone and oestradiol production. Taken together, the present results indicate a direct stimulatory effects of T3 on basal production of testosterone and oestradiol by Leydig cells and its modulatory effect on LH mediated steroidogenic activity varies depending upon the intensity of LH stimuli.

Leydig cell steroidogenic activity under basal and stimulated conditions was studied in hypothyroid rats. Hypothyroidism was induced at a prepubertal age (30 days postpartum) by surgical thyroidectomy, and L-thyroxine (T4) supplementation (6 micrograms/100 g body weight/day for 30 days) to hypothyroid rats was begun after 30 days. Hypothyroidism for 60 days reduced serum LH and FSH without affecting prolactin. Serum and intratesticular testosterone and the specific activity of Leydig cell 3 beta- and 17 beta-hydroxysteroid dehydrogenases diminished in hypothyroid rats. The stimulatory effect of LH on Leydig cell steroidogenic activity and cAMP was also adversely affected in hypothyroid rats. All these changes were reversed by T4 supplementation. The present results suggest that prepubertal hypothyroidism suppresses both basal and stimulated Leydig cell activity in adult rats.

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