Cortisol, pregnene and pregnane profiles in normal and dysmature newborn pony and lighthorse foals

approved: Redacted for Privacy In order to study normal and abnormal progestin biosynthesis, 15 newborn lighthorse and pony foals (325 to 358 d gestation) were either given synthetic ACTH (.2 IU/kg BW, i.v., n = 3), ACTH together with a 3Bhydroxysteroid dehydrogenase blocker (trilostane) (10 mg/kg BW, p.o., n = 7), or no treatment (n = 5) at 4 h of age. Plasma samples were taken from birth through 96 h of age and assayed for cortisol by radioimmunoassay, and for pregnenolone, 5-pregnene-36,20B-diol (P5BB), 5-pregnene38,20a-diol (P5Ba), progesterone, 5a-pregnane-38,20B-diol (5a-DHP-BB), 5a-pregnane-38,20a-diol (5a-DHP-Ba), 38hydroxy-5a-pregnan-20-one (38-0H-5a-DHP) and 20B-hydroxy4-pregnen-3-one (20B-P4) by gas chromatography/mass spectrometry. Preliminary comparisons demonstrated no significant differences in cortisol or progestin concentrations between normal foals given ACTH and ACTH/trilostane treatments and these groups were combined for statistical purposes. In normal foals cortisol increased from birth (99.54 ± 7.44 ng/ml, mean ± SE) to maximum (124.18 ± 28.89 ng/ml) within 1 h of birth and rapidly declined, increasing again if treated with ACTH (129.04 ± 14.23 vs 24.11 ± 2.72 ng/ml at 6 h, for ACTH and normals, respectively) (P < .05); cortisol was below 11 ng/ml by 48 h. Pregnenolone, 5a-DHP-BB, 5a-DHP-Ba, and 3B-OH-5a-DHP were maximal at birth in normal foals (2.32 ± .39, 1.16 ± .68, .75 ± .40, .41 ± .07 gg/ml, respectively) with P5Ba maximum at 2 h (.51 ± .09 gg/ml) and P5BB maximum at 4 h (6.30 ± 1.39 pg/m1). All progestins gradually decreased through 24 h in normal foals; ACTH treatment had no effect on progestin concentrations (P > .05). Three dysmature foals (336 to 352 d gestation) had lower (P < .001) cortisol at birth (25.17 ± 8.66 ng/ml) and failed to respond to ACTH (P < .05); cortisol later increased and remained elevated through 48 h (31.98 ± 10.87 ng/ml) (P < .05). In dysmature foals P5, P5BB and P5Ba concentrations were lower (P > .05) at birth than normal foals, but steadily increased to a maximum of 2 to 8 times normal values at 24 and 48 h. Concentrations of 5a-DHP-BB were not different at birth (P > .05), but 12 times higher in dysmature vs normal foals (3.31 ± .16 vs .21 ± .17 gg/ml at 24 h. 5a-Pregnane-38,20a-diol and 3BOH-5a-DHP gradually declined but tended to remain higher than normal in dysmature animals only. 20B-Hydroxy-4pregnen-3-one was elevated in dysmature animals only. Progesterone was not detected in either normal or dysmature foals. Data suggest that in normal foals cortisol production declines and progestins clear rapidly from circulation within the first 48 h. Dysmature foals demonstrate lower cortisol and progestin values at birth and elevated progestins, especially 206-hydroxylated compounds, at 24 to 48 h. These aberrations in steroid metabolism may be due to enzymatic deficiencies, adrenal disfunction, impaired hepatic and(or) renal clearance or possibly organ immaturity. Further study is needed to determine specific causes before clinical treatments can be developed and evaluated for treatment of dysmaturity. Cortisol, Pregnene and Pregnane Profiles in Normal and Dysmature Newborn Pony and Lighthorse Foals