Effect of dose and route of administration of ACTH _1–24 on plasma Cortisol concentrations in ewes

Abstract

Doses of 0.005-1.0 mg of ACTH1-24 given intravenously, intramuscularly or as an intramuscular depot injection caused increases in cortisol concentrations within 15 min in the plasma of ewes. There was, however, considerable animal-to-animal variation in maximum concentrations achieved. A curvilinear dose-response relationship to ACTH1-24 was obtained which was similar for each route of administration when expressed in terms of maximum cortisol concentrations. However, for a given dose, more prolonged release of cortisol occurred after i.m. injection compared to i.v., with maximum concentrations occurring 6 h after the depot formulation injection. Five repeated daily doses of 1.0 mg depot ACTH1-24 resulted in no diminution of cortisol response indicating considerable synthesizing capacity of the adrenals in clinically normal ewes. Comparison of cortisol concentrations after an acute stressor (shearing) suggests that doses of ACTH1-24 greater than 0.25 mg are excessive for simulation of stress-induced adrenal activity.

Identification of Stimulatory and Inhibitory Inputs to the Hypothalamic‐Pituitary‐Adrenal Axis During Hypoglycaemia or Transport In Ewes

“…Samples were collected over 10 min rather than sampled at single point every 10 min and thus differences in when major changes to ACTH and cortisol occurred during these sampling windows between experiments may account for differences in correlation between samples in each model. Data on the relationship between ACTH concentration and cortisol secretory rate are sparse but plasma cortisol concentration in sheep has been related to the logarithm of ACTH concentration during CRH ± vasopressin infusion (38) and peak cortisol concentration was also related to log ACTH dose (65). The adrenal steroid response to ACTH is integrative as well as proportional.…”

“…If ACTH concentration increased above a threshold (suggested to be 230 pg/ml, which occurred during most of the response to both stimuli), plasma corticosteroid reached a plateaux and higher concentrations of ACTH prolonged the corticosteroid plateaux as steroidogenesis became the rate limiting step (66, 67). The integrative effect was not total because some secretory stimulus was lost when the concentrations were above threshold (65). Inclusion of ACTH variables from previous times in the models may represent stimulus duration to reflect this relationship.…”

Effects of Administration of Adrenocorticotrophic Hormone (ACTH) on Extragonadal Progesterone Levels in Sheep

“…Although the precise mechanism has not been elucidated, one hypothesis is that the stress-induced release of adrenocorticotrophin (ACTH) and subsequent glucocorticoid secretion interferes with the release of gonadotrophins through action on the hypothalamus and/or the adenohypophysis (Moberg 1976;Moberg et al 1981). Cortisol is the predominant glucocorticoid in sheep plasma (Bush and Ferguson 1953) and has been used as a reliable physiological endpoint for determining the response of the adrenal cortex to stress (Essawy et al 1989). However, the role of cortisol in reproductive failure is still not clear.…”

Physiological and Endocrine Factors Contributing to Acyclicity in the Captive Female African Elephant (Loxodonta africana)

“…Adrenal-produced cortisol secreted during times of stress is a known suppressor of GnRH from the hypothalamus (Ringstrom and Shwartz, 1987). Increased glucocorticoid secretion near the onset of estrus in the cow, ewe, and sow can block the ovulatory surge in LH and ovarian steroidogenesis (Essawy et al, 1989), suppress PGF 2α subsequently prolonging the estrous cycle in ruminants (Abilay et al, 1975;Liptrap, 1993), and retard follicular development at the time of emergence of the ovulatory cohort in the sow (Liptrap, 1970;Barb et al, 1982). During the normal estrous cycle, GnRH from the hypothalamus acts at the pituitary level to initiate the secretion of gonadotropins, FSH and LH.…”