LifeTideSW5 is a growth hormone-releasing hormone (GHRH)-expressing plasmid delivered by intramuscular (IM) electroporation (EP), and the first therapeutic plasmid delivered by this physical method to be approved for use in food animals. Gestating sows (n = 997) were treated once with a single 5-mg GHRH-plasmid by EP or served as controls. Data on offspring from three parities subsequent to treatment were collected. No adverse effects related to treatment were noted. First parity post-treatment offspring from treated sows displayed a 2.93 kg (P < 0.0001) increase in carcass weight (CW), 1.0 mm (P < 0.0001) less back-fat (P2), and a 27.0 g CW/day (P < 0.0001) increase in rate of gain (ROG) compared with controls. An increase of 21.6% was recorded in the number of offspring surviving. In the second and third parities post-treatment, offspring from treated females displayed higher number of born alive and total born number, and lower stillborn rates. Third parity offspring from treated sows displayed a 1.6 kg advantage in CW (P < 0.05), 1.0 mm less P2 (P < 0.05), and a 10.0 g CW/day benefit in ROG. Furthermore, offspring from treated females had a 19.04% lower post-wean loss rate. Overall, plasmid GHRH administration decreased morbidity and mortality in treated females and their offspring over three consecutive pregnancies.

Metyrapone (MET) inhibition of hydrocortisone (³H-HC) uptake and binding in the cytosol and nucleus of various brain regions of the pig was demonstrated in vivo. The hippocampus, hypothalamus and septum were the regions most sensitive to the inhibition by MET. The hippocampus exhibited the greatest reduction in ³H-HC concentration in whole homogenate, bound in cytosol and in nuclei. The anterior pituitary and cerebral cortex were the least sensitive to MET. In vitro incubation of hypothalami with ³H-HC and MET substantiated the results obtained in vivo with regard to the inhibitory action of MET on ³H-HC uptake and binding. These results were interpreted to indicate that MET may act directly in certain brain regions and that this inhibitory action has important implications for both experimental and clinical uses of this drug.

Dogs were bilaterally adrenalectomized (Adx) or sham adrenalectomized 2 weeks after the administration·6-hydroxydopamine (6-OHDA) or saline-ascorbic acid vehicle directly into the third ventricle (3V). Hypothalamic and hippocampal cytosols were assayed in vitro for high affinity binding of ³H-dexamethasone (³H-DM). 6-OHDA treatment resuited in a significant reduction of norepinephrine concentration in the hypothalamus, but not in the hippocampus, when measured 2 weeks after the second dose. Treatment with this neurotoxin also caused a decrease in ³H-DM binding in the hy pothalamus that was detectable after adrenalectomy. A statistically significant reduction in bound DM was not observed in the hypothalamus after 6-OHDA treatment of dogs with intact adrenals, perhaps because of a masking effect of endogen pus corticosteroids. No change was observed in the hippocampus. Saturation analysis of binding data revealed the total maximum number of available binding sites in hypothalamic cytosol was lower after 6-OHDA treatment, compared to saline-injected controls. Calculated values for dissociation constants revealed no differences between dogs treated with Adx saline and Adx, and 6-OHDA. The data support the suggestion that catecholamines may act, in part, by altering the specific binding of a glucocorticoid to its hypothalamic receptor.