Repeated administrations of adrenocorticotropic hormone during late gestation in pigs: Maternal cortisol response and effects on fetal HPA axis and brain neurotransmitter systems

• Published in: Theriogenology 2008-02, Vol.69 (3), p.312-322
• Main Authors: Otten, W., Kanitz, E., Tuchscherer, M., Brüssow, K.-P., Nürnberg, G.
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptamine; ACTH; Adrenal Glands - drug effects; Adrenal Glands - embryology; Adrenocorticotropic Hormone - administration & dosage; animal stress; Animals; Biogenic Monoamines - analysis; blood glucose; Blood Glucose - analysis; Brain - drug effects; Brain - embryology; Brain Chemistry - drug effects; corticotropin; cortisol; Female; fetus; Gestational Age; Glucocorticoid receptor; glucocorticoid receptors; hippocampus; hormone receptors; hormone secretion; Hydrocortisone - blood; hypothalamic-pituitary-adrenocortical axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - embryology; hypothalamus; Insulin - blood; insulin secretion; intramuscular injection; Kinetics; Male; Maternal-Fetal Exchange; Neurotransmitter Agents - physiology; neurotransmitters; Pigs; Pregnancy; Prenatal stress; Receptors, Glucocorticoid - metabolism; serotonin; Sex Characteristics; sows; Swine - embryology; Swine - physiology; Umbilical Arteries; Umbilical Veins
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2007.09.025

The present study examined the effects of repeated adrenocorticotropic hormone (ACTH) administrations to sows during late gestation on hypothalamic-pituitary-adrenocortical (HPA) axis and brain neurotransmitter systems in their fetuses. ACTH (100 IU per animal, Synacthen ® Depot, n = 6) or saline ( n = 5) was administered intramuscularly to sows every 2nd day from gestational day (GD) 85 to GD 101. Blood samples were taken from sows repeatedly within 12 h after ACTH application on GD 85 and GD 101. On GD 105, fetuses were recovered under general anaesthesia for the collection of blood and brain samples. Plasma cortisol concentrations in sows increased significantly within 2 h after ACTH application and returned to control levels after 10 h post-application, showing a similar response at the beginning and at the end of the 16-day stimulation period. On GD 101, a significant increase of plasma glucose and insulin concentrations was found in sows after administration of ACTH and after a following feeding time. Number and body weight of fetuses were not affected by the maternal ACTH treatment. Cortisol concentrations in the umbilical vein were significantly decreased in fetuses from ACTH sows and a similar trend was observed in the umbilical artery and in the vena cava cranialis. Glucocorticoid receptor (GR) binding in hippocampus and hypothalamus did not differ between treatments. However, in hippocampus, serotonergic activity was increased in fetuses from ACTH-treated mothers as shown by significantly elevated 5-hydroxytryptamine (5-HT) levels. In conclusion, repeated administrations of ACTH during late gestation resulted in a reproducible cortisol response of sows and reduced cortisol concentrations in the fetal umbilical vein after the treatment period. Although the number of sows used in this experiment was low and differences between treatments were limited these findings indicate that excessive glucocorticoid exposure during gestation alters serotonergic activity in hippocampus of fetuses and may affect the emotional reactivity later in life.