Myostatin regulates pituitary development and hepatic IGF1.

Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice. This correlated with increased levels of GH, prolactin, and the cells that secrete these hormones, somatotropes and lactotropes, respectively, in Jekyll pituitaries. Recombinant myostatin also stimulated GH release and gene expression in pituitary cell cultures although inhibiting prolactin release. In primary hepatocytes, recombinant myostatin blocked GH-stimulated expression of two key mediators of growth, insulin-like growth factor (IGF)1 and the acid labile subunit and increased expression of an inhibitor, IGF-binding protein-1. The significance of these findings was demonstrated by smaller muscle fiber size in a model lacking myostatin and liver IGF1 expression (LID-o-Mighty mice) compared with that in myostatin-null (Mighty) mice. These data together suggest that myostatin may regulate pituitary development and function and that its inhibitory actions in muscle may be partly mediated by attenuating GH action in the liver. They also suggest that circulating pharmacological inhibitors of myostatin could produce unintended consequences in these and possibly other tissues.

Household transmission of SARS-CoV-2 from humans to pets in Washington and Idaho: burden and risk factors.

SARS-CoV-2 is believed to have emerged from an animal reservoir; however, the frequency of and risk factors for inter-species transmission remain unclear. We carried out a community-based study of pets in households with one or more confirmed SARS-CoV-2 infection in humans. Among 119 dogs and 57 cats with completed surveys, clinical signs consistent with SARS-CoV-2 were reported in 20 dogs (21%) and 19 cats (39%). Out of 81 dogs and 32 cats sampled for testing, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive; this discordance may be due to delays in sampling. Respondents commonly reported close human-animal contact and willingness to take measures to prevent transmission to their pets. Reported preventative measures showed a slightly protective trend for both illness and seropositivity in pets, while sharing of beds and bowls had slight harmful effects.

Serum Melatonin Values in Normal Dogs and Dogs with Seizures.

Epilepsy, or recurrent seizures, is reported to be the most common neurologic condition in dogs; 20-30% of epileptic dogs are considered to be pharmacoresistent to one medication. The hormone melatonin has been shown to have significant anticonvulsant effects; epileptic humans have lower serum melatonin levels than unaffected individuals. We hypothesize that serum levels of melatonin will be lower in dogs with seizures as compared with normal dogs. Sixty-two dogs were enrolled in the study: 29 normal dogs (Group 1) and 33 dogs with seizures (Group 2). Blood sampling was done at three separate time points (8:00 a.m., 12:00, and 4:00 p.m.). The majority of dogs in Groups 1 (69%) and 2 (76%) had serum melatonin levels <0.5 pg/mL as measured by radioimmunoassay. There were no significant differences in serum melatonin values between the groups or within groups when time of blood draw, length of sample freezing, time of day/year of sampling, or presence of anticonvulsant therapy were compared. There were no notable differences in daytime serum melatonin values in normal dogs versus dogs with seizures. The majority of daytime serum melatonin levels were <0.5 pg/mL in dogs with and without seizures.

Evaluation of a serum ELISA for detection of bovine leukemia viral antibodies in milk samples.

Bovine leukemia virus (BLV) infection has worldwide distribution in both dairy and beef herds. Our study was initiated in order to encourage control of BLV infection by using milk samples, in lieu of serum samples, to readily test lactating animals prior to dry-off and calving. Two Holstein dairy herds (A and B), with known status of BLV infection as determined by serology, were sampled by the collection of serum and fresh milk samples. Selected samples were tested using a USDA-licensed BLV antibody ELISA kit (Bovine leukemia virus antibody test kit; VMRD, Pullman, WA) for serum. Forty-one lactating cows from each herd were sampled. Herd A was confirmed to have endemic BLV infection; herd B was confirmed to be free of BLV infection. The milk ELISA results demonstrated 100% identification of positive and negative animals compared with the serum results. The correlation of the ELISA values between serum and milk samples was 97%, which supports the use of this BLV ELISA on milk samples.

Testicular development, ultrasonographic and histological appearance of the testis in ram lambs immunized against recombinant LHRH fusion proteins.

Sixteen native ram lambs weaned at 10 wk of age were divided into two groups. Eight animals were immunized against LHRH with a mixture of two fusion proteins: ovalbumin-LHRH-7 and thioredoxin-LHRH-7. The immunized lambs received a primary immunization plus two booster immunizations at 4 and 12 wks. Animals in the control group (n=8) were not treated. Scrotal measurements and blood samples were taken at 2-week intervals. Beginning at 25 wk of age, semen was collected and sexual behaviour was evaluated on a weekly basis. At 35 and 37 wk of age testes and accessory glands of all animals were subjected to ultrasound scanning. At 37 wk of age animals were slaughtered and testes were evaluated histologically. Serum LHRH antibodies (P<0.01) were detected in animals of the immunized group which had reduced serum testosterone concentrations (P<0.01). Testicular development was suppressed in the immunized animals (P<0.01). Immunized animals exhibited mounting activity 5 wks later than control animals. No mature spermatozoa containing ejaculates were collected from immunized animals. Control animals had moderately echogenic ultrasonographic appearance at 37 wk age, whereas immunized animals had hypoechogenic images. Mean seminiferous tubule diameter in immunized lambs was significantly smaller than that in control lambs. Basal membrane was thickened and hyalinized; there was an increase in peritubular connective tissue. No proliferating spermatogonia or mature spermatozoa were present in the tubules in these animals. There were no differences in the ultrasonographic appearance of prostate and vesicular gland between control and immunized animals. The LHRH recombinant fusion proteins were effective in immunological castration in ram lambs when started at 10 wk of age as noted by differences in serum testosterone, testicular histology and ultrasonographic appearance of testis and weight of accessory sex glands. Determining the effects of immunization on ultrasonographic appearance of the testis related to time after immunization requires further investigations.