Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 27, 2003
Publication Date: April 1, 2004
Citation: Barb, C.R., Barrett, J.B., Kraeling, R.R. 2004. Role of leptin in modulating the hypothalamic-pituitary axis and luteinizing hormone secretion in the prepuberal gilt. Domestic Animal Endocrinology. 2004. v. 26. p. 201-214. Interpretive Summary: Inadequate nutrition is characterized by low blood levels of pituitary hormones, such as luteinizing hormone (LH), that are necessary for stimulation of the reproductive system. A lack of these hormones results in delayed puberty, irregular heat cycles and failure of animals to breed. The recently discovered protein, leptin, secreted by fat cells in response to changes in body weight or energy, stimulates metabolism, LH secretion and accelerates puberty in rodents. Leptin may serve as a signal linking the body's energy regulating system with the reproductive system. This is the first report to demonstrate that administration of leptin stimulated LH secretion from pig pituitary cells in culture and gonadotropin releasing hormone (GnRH, brain hormone that stimulates LH secretion) from brain tissue in culture but did not affect neuropeptide Y (NPY; brain peptide that inhibits GnRH release). Therefore, understanding the leptin - GnRH/LH interactions is necessary in order to develop new methods to accelerate puberty and improved reproductive efficiency in the breeding herd.
Technical Abstract: In experiment I (EXP), prepuberal gilts received intracerebroventricular (ICV) leptin (LEP) injections. Blood was collected 4h before and 3h after ICV inj. of .9% saline (S; n=3), 10 ug (n=4), 50 ug (n=4) or 100 ug (n=4) of LEP in S. EXP II, pituitary cells in culture were challenged with 0.1 nM, 1 nM, 10 nM, or 100 nM, gonadotropin releasing hormone (GnRH), 0.01 pM, 0.1 pM, 1 pM, 10 pM, 100 pM, 0.01 uM, 0.1 uM or 1 uM LEP individually or in combinations with 0.1, 1nM and 10 nM GnRH. LH was measured at 4 h. Exp III, hypothalamic-preoptic area was removed and halved and placed in chambers. Fractions were collected every 5 min. Explants were exposed to 0 (n = 5), 1pM (n = 4), 100 pM (n = 4), 10 nM (n = 4) or 1 uM (n = 5) LEP for 30 min. EXP I, serum LH levels were unaffected by LEP. EXP II, LH secretion (control; n=12wells) was 4.7 ± 0.4 ng/well. Relative to control at 4 h, 1 nM, 10 nM, and 100 nM GnRH increased (P<0.001) LH secretion. All doses of LEP increased (P<0.05) LH secretion except for 1 pM and 1 nM. Addition of 100 nM or 0.1 pM LEP in combination with 10 nM or 1 nM GnRH suppressed (P<0.05) LH secretion. However, 1, 10 and 100 pM LEP in combination with 1 nM GnRH or 10 or 100 pM LEP in combination with 10 nM GnRH failed to alter LH response to GnRH. In contrast, 10 and 100 pM LEP increased (P<0.05) LH response to 0.1 nM GnRH. EXP III, prior to LEP, GnRH secretion averaged 45 ± 1 pg/fraction across. GnRH concentrations increased (P<0.05) after 1pM (60 ± 4 pg/fraction),100 pM (96 ± 4 pg/fraction) and 10 nM (81 ± 4 pg/fraction) compared to control (46 ± 4 pg/fraction). GnRH secretion was unaffected by 1 uM of leptin. Leptin treatment failed to influence NPY. These results indicate that LEP directly modulates LH secretion from the pituitary gland and GnRH release from the hypothalamus.