Effect of endotoxin on the expression of GnRH and GnRHR genes in the hypothalamus and anterior pituitary gland of anestrous ewes

Abstract

An immune/inflammatory challenge can affect reproduction at the level of the hypothalamus, pituitary gland, or gonads. Nonetheless, the major impact is thought to occur within the brain or the pituitary gland. The present study was designed to examine the effect of intravenous (i.v.) lipopolysaccharide (LPS) injection on the expression of gonadotropin-releasing hormone (GnRH) and the gonadotropin-releasing hormone receptor (GnRHR) genes in the hypothalamic structures where GnRH neurons are located as well as in the anterior pituitary gland (AP) of anestrous ewes. We also determined the effect of LPS on luteinizing hormone (LH) release. It was found that i.v. LPS injection significantly decreased GnRH and GnRHR mRNAs levels in the preoptic area (40%, p ≤ 0.05 and 60%, p ≤ 0.01 respectively) and median eminence (50% and 50% respectively; p ≤ 0.01). Endotoxin injection decreased plasma LH concentration (25%; p ≤ 0.05) and GnRHR gene expression (80%, p ≤ 0.01) in the AP. Together, these observations indicate that inflammatory challenge can affect the reproductive system at the hypothalamic level through modulation of the activity of GnRH-ergic neurons as well as at the level of the AP via inhibition of LH secretion or/and through reduction of the sensitivity of GnRH reactive pituitary cells to GnRH stimulation. The presence of GnRH mRNA in the median eminence, the hypothalamic structure where GnRH-ergic neurons’ terminals are located, suggests that the axonal transport of GnRH mRNA may occur in these neurons. This phenomenon could play an important role in the physiology of GnRH neurons. Our data demonstrate that immune stress could be important inhibitor of this process.