The hypothalamus links the brain to the endocrine system by producing hormones that travel in short blood vessels directly to the pituitary. The pituitary responds by secreting hormones which act on target organs to regulate body functions important in health and disease, e.g. growth, reproduction, metabolic rate, responses to stress and pain, etc. The main barrier to understanding how the brain controls, these functions, and how external and internal perturbations upset this control, has been the inability to measure hypothalamic hormones in the living animal, without using the destructive, terminal surgery needed to sample from the deeply situated vessels that transport these hormones. To solve this problem, the applicants have developed, and are successfully applying, an original technique for collecting pituitary venous blood from conscious, unrestrained horses. This requires only puncture of a subcutaneous vein for insertion of a cannula which is carefully manipulated along venous pathways, unique to the horse, until its tip lies at the outlet of the pituitary vein. Using this technique, large (4-8 ml), frequent (@ 2 min) samples, containing accurately measurable levels of hypothalamic and pituitary hormones, can be collected from normally functioning animals for at least a week. The proposed project uses this animal model to study release patterns and secretion rates of hypothalamic and pituitary hormones regulating the adrenal and thyroid axes under basal conditions and after various stresses commonly encountered by the human and other species. The effects of experimental removal and replacement of gonadal, adrenal and thyroid hormones on hypothalamic hormones secretion will be measured, for the first time in normal subjects, to investigate the central effects of widely used hormone and antihormone therapy. These experiments will test hypotheses suggested by indirect and in vitro studies. This project should provide basic information, unobtainable by any other method, on the brain's hormonal control of the body, which could find widespread application in human and veterinary medicine in areas ranging from fertility control to stress management.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK038322-01A1
Application #
3237643
Study Section
Reproductive Biology Study Section (REB)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Lincoln University
Department
Type
DUNS #
592214472
City
Canterbury
State
Country
New Zealand
Zip Code
8000
Alexander, S L; Roud, H K; Irvine, C H (1997) Effect of insulin-induced hypoglycaemia on secretion patterns and rates of corticotrophin-releasing hormone, arginine vasopressin and adrenocorticotrophin in horses. J Endocrinol 153:401-9
Irvine, C H; Alexander, S L (1997) Patterns of secretion of GnRH, LH and FSH during the postovulatory period in mares: mechanisms prolonging the LH surge. J Reprod Fertil 109:263-71
Alexander, S L; Irvine, C H; Donald, R A (1996) Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses. Front Neuroendocrinol 17:1-50
Alexander, S L; Irvine, C H (1995) The effect of naloxone administration on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses. Endocrinology 136:5139-47
Irvine, C H; Alexander, S L (1994) The dynamics of gonadotrophin-releasing hormone, LH and FSH secretion during the spontaneous ovulatory surge of the mare as revealed by intensive sampling of pituitary venous blood. J Endocrinol 140:283-95
Irvine, C H; Alexander, S L (1994) Factors affecting the circadian rhythm in plasma cortisol concentrations in the horse. Domest Anim Endocrinol 11:227-38
Alexander, S L; Irvine, C H; Donald, R A (1994) Short-term secretion patterns of corticotropin-releasing hormone, arginine vasopressin and ACTH as shown by intensive sampling of pituitary venous blood from horses. Neuroendocrinology 60:225-36
Alexander, S L; Irvine, C H; Livesey, J H et al. (1993) The acute effect of lowering plasma cortisol on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin as revealed by intensive sampling of pituitary venous blood in the normal horse. Endocrinology 133:860-6
Irvine, C H; Alexander, S L (1993) Secretory patterns and rates of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone revealed by intensive sampling of pituitary venous blood in the luteal phase mare. Endocrinology 132:212-8
Shand, N; Alexander, S L; Irvine, C H (1991) Comparison of the microheterogeneity of horse LH and FSH in the pituitary with that secreted into pituitary venous blood at oestrus. J Reprod Fertil Suppl 44:1-11

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