Testosterone Propionate

The objective of this study was to investigate the impact of partially substituting whole corn silage (CS) with sweet sorghum silage (SS) on serum metabolites in dairy cows employing by Liquid chromatography-mass spectrometry (LC-MS). Thirty mid-lactation Holstein dairy cows (112 ± 24.04 days in milk) were divided into the control group (CON) received 40% CS and 0% SS, Group1 received 30% CS and 10% SS, while Group2 received 20% CS and 20% SS, respectively. Serum samples were collected on day 45 of the formal experiment and subjected to LC-MS analysis to detect metabolites. The results revealed that 29 different metabolites were obtained in both CON and Group1; however, 22 metabolites in Group1 showed up-regulation compared to those in CON including N-Methylhydantoin, Betaine, Isoleucine, etc. The levels of 7 metabolites, including L-Kynurenine, Nandrolone, and Testosterone propionate, were found to be down-regulated. Sixteen metabolites were detected in the serum of Group2 and CON dairy cows. Compared with CON, Group2 exhibited up-regulation of 13 metabolites such as Benzaldehyde, Linoleic acid, Phe-Glu. Conversely, three metabolites including Triglycerides (TG), Uric acid and 5-Hydroxyindole-3-acetic acid showed down-regulation. A total of 20 differential metabolites were identified in Group1 and Group2. Among these, 14 metabolites such as 2-Ethylacrylic acid, Succinic acid, and Glutamic acid were up-regulated while 6 metabolites like Pyridoxine, Phosphocholine, and Quinidine showed down-regulation. These differentially expressed metabolites are primarily associated with various pathways including Aminoacyl-tRNA, Arginine, Phenylalanine and tryptophan biosynthesis, Citrate cycle etc. In conclusion, substituting up to 50% of CS with SS had no negative effects on serum metabolites, indicating that SS can partially replace CS in the diets of high-producing lactating dairy cows without adding extra grain, when diets are fed for a short time under our feeding experimental conditions.

Sex differences in pain perception and response to analgesics are well documented, yet the underlying causes remain poorly understood. Here we investigate the sexual dimorphism in the function of α₆GABA_A receptors in neuropathic pain, focusing on activational and organizational actions of gonadal hormones. Using the nerve ligation model in rats, we found that the positive allosteric modulator, PZ-ll-029 (30 nmol, it), produced a robust antiallodynic effect in females but not in males. Ovariectomy abolished this effect, while a single dose of estradiol (20 μg/kg sc, -24 h), that returned to physiological serum levels, partially restored it, indicating that the activational effect of estradiol is crucial for α₆GABA_A receptor-mediated antiallodynia in females. Interestingly, adult or neonatal (at postnatal day 3) orchidectomy did not alter the male's insensitivity to PZ-ll-029, even after estradiol treatment. However, neonatal female's virilization (with testosterone propionate 120 μg/rat at postnatal day 3) induced a male-like insensitivity to PZ-ll-029, that was partial when the ovaries were present and complete after adult ovariectomy. These findings reveal that the neonatal organizational effects of testosterone determine the sex-specific insensitivity of α₆GABA_A receptors to modulate neuropathic pain, while the activational effects of estradiol can partly maintain the female-typical response, despite early androgen exposure. Our results provide new insights into hormonal regulation of pain modulation and suggest that both developmental exposure and adult status should be considered in basic research and preclinical studies investigating sex-based dimorphisms.