Thyrotropin releasing hormone interactions with growth hormone secretion in horses.

Light horse mares, stallions, and geldings were used to 1) extend our observations on the thyrotropin releasing hormone (TRH) inhibition of GH secretion in response to physiologic stimuli and 2) test the hypothesis that stimulation of endogenous TRH would decrease the normal rate of GH secretion. In Exp. 1 and 2, pretreatment of mares with TRH (10 microg/kg BW) decreased (P < 0.001) the GH response to exercise and aspartate infusion. Time analysis in Exp. 3 indicated that the TRH inhibition lasted at least 60 min but was absent by 120 min. Administration of a single injection of TRH to stallions in Exp. 4 increased (P < 0.001) prolactin concentrations as expected but had no effect (P > 0.10) on GH concentrations. Similarly, 11 hourly injections of TRH administered to geldings in Exp. 5 did not alter (P > 0.10) GH concentrations either during the injections or for the next 14 h. In Exp. 5, it was noted that the prolactin and thyroid-stimulating hormone responses to TRH were great (P < 0.001) for the first injection, but subsequent injections had little to no stimulatory effect. Thus, Exp. 6 was designed to determine whether the inhibitory effect of TRH also waned after multiple injections. Geldings pretreated with five hourly injections of TRH had an exercise-induced GH response identical to that of control geldings, indicating that the inhibitory effect was absent after five TRH injections. Retrospective analysis of pooled, selected data from Exp. 4, 5, and 6 indicated that endogenous GH concentrations were in fact lower (P < 0.01) from 45 to 75 min after TRH injection but not thereafter. In Exp. 7, 6-n-propyl-2-thiouracil was fed to stallions to reduce thyroid activity and hence thyroid hormone feedback, potentially increasing endogenous TRH secretion. Treated stallions had decreased (P < 0.01) concentrations of thyroxine and elevated (P < 0.01) concentrations of thyroid-stimulating hormone by d 52 of feeding, but plasma concentrations of GH and prolactin were unaffected (P > 0.10). In contrast, the GH response to aspartate and the prolactin response to sulpiride were greater (P < 0.05) in treated stallions than in controls. In summary, TRH inhibited exercise- and aspartate-induced GH secretion. The duration of the inhibition was at least 1 h but less than 2 h, and it waned with multiple injections. There is likely a TRH inhibition of endogenous GH episodes as well. Reduced thyroid feedback on the hypothalamic-pituitary axis did not alter basal GH and prolactin secretion.

Effects of dexamethasone, glucose infusion, adrenocorticotropin, and propylthiouracil on plasma leptin concentrations in horses.

In experiment 1, nine light horse geldings (three 3 x 3 Latin squares) received dexamethasone (DEX; 125 microg/kg BW, i.m.), glucose (0.2 g/kg BW, i.v.), or nothing (control) once per day for 4 days. DEX increased (P < 0.001) glucose, insulin, and leptin concentrations and resulted in a delayed increase (P < 0.001) in IGF-I concentrations. In experiment 2, mares were similarly treated with DEX (n = 6) or vehicle (n = 6). DEX again increased (P < 0.01) glucose, insulin, and leptin concentrations; the delayed elevation in IGF-I concentrations occurred on day 10, 12, and 19, relative to the first day of treatment. In experiment 3, six light horse geldings received either 200 IU of adrenocorticotropin (ACTH) i.m. or vehicle twice daily for 4 days. ACTH increased (P < 0.001) cortisol concentrations. Further, ACTH resulted in increases (P < 0.01) glucose, insulin, and leptin concentrations. In experiment 4, plasma samples from four light horse stallions that were fed 6-n-propyl-2-thiouracil (PTU) at 6 mg/kg BW for 60 days to induce hypothyroidism were compared to samples from control stallions. On day 52, stallions receiving PTU had lower concentrations of thyroxine (P < 0.05) and triiodothyronine (P < 0.01) and higher (P < 0.01) concentrations of TSH. Leptin concentrations were higher (P < 0.01) in PTU-fed stallions from day 10 through 52. In conclusion, circulating concentrations of leptin in horses was increased by administering DEX. Treatment with ACTH increased cortisol and resulted in lesser increases in leptin, glucose, and insulin. In addition, PTU feeding results in lesser increases in leptin concentrations.

Growth hormone response to a novel growth hormone-releasing tripeptide in horses: interaction with gonadotropin-releasing hormone, thyrotropin-releasing hormone, and sulpiride.

A series of experiments was performed to determine the factor(s) responsible for an apparent inhibition of GH secretion in mares administered the GH secretagogue EP51389 in combination with GnRH, thyrotropin-releasing hormone (TRH), and sulpiride. Experiment 1 tested the repeatability of the original observation: 10 mares received EP51389 at 10 microg/kg BW; five received TRH (10 microg/kg BW), GnRH (1 microg/kg BW), and sulpiride (100 microg/kg BW) immediately before EP51389, and five received saline. The mixture of TRH, GnRH, and sulpiride reduced (P = 0.0034) the GH response to EP51389, confirming the inhibitory effects. Experiment 2 tested the hypothesis that sulpiride, a dopamine antagonist, was the inhibitory agent. Twelve mares received EP51389 as in Exp. 1; six received sulpiride before EP51389 and six received saline. The GH responses in the two groups were similar (P > 0.1), indicating that sulpiride was not the inhibitory factor. Experiment 3 tested the effects of TRH and(or) GnRH in a 2 x 2 factorial arrangement of treatments. Three mares each received saline, TRH, GnRH, or the combination before EP51389 injection. There was a reduction (P < 0.0001) in GH response in mares receiving TRH, whereas GnRH had no effect (P > 0.1). Given those results, Exp. 4 was conducted to confirm that TRH was inhibitory in vivo as opposed to some unknown chemical interaction of the two compounds in the injection solution. Twenty mares received TRH or saline and(or) EP51389 or saline in a 2 x 2 factorial arrangement of treatments. Injections were given separately so that the two secretagogues never came in contact before injection. Again, TRH reduced (P < 0.0001) the GH response to EP51389. In addition, TRH and EP51389 each resulted in a temporary increase in cortisol concentrations. Experiment 5 tested whether TRH would alter the GH response to GHRH itself. Twelve mares received porcine GHRH at 0.4 microg/kg BW; six received TRH prior to GHRH and six received saline. After adjustment for pretreatment differences between groups, the GHRH-induced GH response was completely inhibited (P = 0.068) by TRH. Exp. 6 was a repeat of Exp. 5, except geldings were used (five per group). Again, pretreatment with TRH inhibited (P < 0.0001) the GH response to GHRH. In conclusion, TRH inhibits the GH response not only to EP51389 but also to GHRH in horses, and in addition to its known secretagogue action on prolactin and TSH it may also stimulate ACTH at the dosage used in these experiments.