Background/Aims: Growth hormone (GH) is necessary for optimal reproductive efficiency and its secretion is influenced by sex steroids. This study was designed to determine whether kisspeptin-10 (Kp10) could stimulate GH and if gonadal steroids enhance the GH response to Kp10 in cows. Methods and Results: Intravenous injection of Kp10 at 100 or 200 pmol/kg body weight with or without treatment with estradiol cypionate and/or progesterone increased luteinizing hormone (p < 0.01) plasma concentrations. Plasma concentrations of GH were increased following Kp10 in cows treated with estradiol cypionate and/or progesterone (p < 0.05) but not in cows treated with Kp10 without gonadal steroids. Conclusions: These data suggest that reproductive steroids enhance the sensitivity of the somatotropic axis to physiologically relevant doses of Kp10, and support the possibility that Kp10 is an integrator of luteinizing hormone and GH release.

Tay-Sachs disease (TSD) is a fatal neurodegenerative disorder caused by a deficiency of the enzyme hexosaminidase A (HexA). TSD also occurs in sheep, the only experimental model of TSD that has clinical signs of disease. The natural history of sheep TSD was characterized using serial neurological evaluations, 7 Tesla magnetic resonance imaging, echocardiograms, electrodiagnostics, and cerebrospinal fluid biomarkers. Intracranial gene therapy was also tested using AAVrh8 monocistronic vectors encoding the α-subunit of Hex (TSD α) or a mixture of two vectors encoding both the α and β subunits separately (TSD α + β) injected at high (1.3 × 10 vector genomes) or low (4.2 × 10 vector genomes) dose. Delay of symptom onset and/or reduction of acquired symptoms were noted in all adeno-associated virus-treated sheep. Postmortem evaluation showed superior HexA and vector genome distribution in the brain of TSD α + β sheep compared to TSD α sheep, but spinal cord distribution was low in all groups. Isozyme analysis showed superior HexA formation after treatment with both vectors (TSD α + β), and ganglioside clearance was most widespread in the TSD α + β high-dose sheep. Microglial activation and proliferation in TSD sheep-most prominent in the cerebrum-were attenuated after gene therapy. This report demonstrates therapeutic efficacy for TSD in the sheep brain, which is on the same order of magnitude as a child's brain.

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Our objective was to determine if prepubertal rate of body weight (BW) gain, independent of diet, was related to mammary development of dairy heifers. Data from two studies recently conducted at Michigan State University were used to identify factors, within a dietary treatment group, that would account for variation in first lactation milk production or amount of mammary parenchymal DNA at the time of puberty. Factors analyzed for variation in milk production during first lactation were: postpartum BW, prepubertal BW gain, gestational BW gain, postpartum BW gain, body condition score (BCS) at breeding, and BCS at calving. Factors analyzed for variation in mammary parenchymal DNA at puberty were: BW at slaughter, age at puberty, prepubertal BW gain and body protein and body fat content at slaughter. For both analyses, prepubertal BW gain did not account for any of the variation in mammary development. The only significant covariate for the milk production model (r2 = 0.44) was BCS at breeding. Similarly, the only significant covariate in the parenchymal DNA model (r2 = 0.22) was body fat content at slaughter. These results suggest that, within a dietary treatment, heifers that grow faster do not have impaired mammary development, and increased body fatness may be a better predictor of impaired mammary development than BW gain.

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