Effect of estrogen on leptin and expression of leptin receptor transcripts in prepubertal dairy heifers

Plasma leptin concentrations increase as growing dairy heifers approach puberty and have greater plasma estrogen. In intact and ovariectomized rodents, estrogen has been shown to modulate expression of leptin and its receptor (Ob-R). To determine if estrogen regulates the bovine leptin system, prepubertal dairy heifers were ovariectomized at 140 d of age or left intact. A month later, both groups received a subcutaneous injection of excipient or 17 beta-estradiol for 3 consecutive days. Neither ovarian status nor 17 alpha-estradiol injection altered plasma leptin or leptin mRNA abundance in adipose tissue depots. To assess whether these factors affected Ob- R expression, we tested 20 bovine tissues for leptin receptor (Ob-R) by using quantitative realtime PCR assays for the short receptor isoform (Ob-Ra), the long receptor isoform (Ob- Rb), and all receptor isoforms Ob-R-TOTAL). Ob-R-TOTAL was detected in all tissues, with copy numbers covering 3 orders of magnitude between the lowest and highest expressing tissues ( kidney cortex vs. liver). The Ob-Rb isoform accounted for 40% of Ob-R-TOTAL in the hypothalamus, but averaged less than 3% of Ob-R-TOTAL in peripheral tissues. Reciprocally, Ob-Ra accounted for only 19% of Ob-R-TOTAL in the hypothalamus and for nearly all of Ob-R-TOTAL in most peripheral tissues. Finally, we evaluated the effects of ovarian status and 17 beta-estradiol on Ob-R expression in selected tissues. Treatment with 17 beta-estradiol reduced Ob-R-TOTAL, Ob-Rb, and Ob- Ra expression by 70% in the uterine endometrium and tended to do the same in mammary adipose tissue. There was no effect of 17 beta-estradiol on Ob-R in the hypothalamus, liver, soleus muscle, or subcutaneous adipose tissue. We conclude that greater estrogen secretion does not cause increased plasma leptin in prepubertal dairy heifers but estradiol can modulate Ob-R expression in some estrogen-responsive tissues.