US22 gene family members m142 and m143 are essential for replication of murine cytomegalovirus (MCMV). Their transcripts are produced with immediate-early kinetics, but little else is known about these viral genes. Unlike their transcripts, the m142 and m143 gene products (pm142, pm143) were not expressed until early times post-infection, with levels increasing over the course of infection. Both pm142 and pm143 were predominantly cytoplasmic, but cellular fractionation studies confirmed that the proteins were present in the nucleus as well. In addition, pm142 was detected within the virion. Both the m142 and m143 promoters were strongly upregulated by viral infection or by MCMV IE1. However, UV-inactivated virus and IE3 upregulated only the m142 promoter. When tested for transcriptional transactivating activity, neither m142 nor m143 demonstrated significant activity, either alone or in combination with the major immediate-early gene products. This failure to transactivate, along with their essential nature, makes m142 and m143 unique among the immediate-early genes of the US22 gene family.

Acute superior cervical ganglionectomy (SCGx) induces in the rat a supraliminal release of neurotransmitter in the innervated tissues (i.e., thyroid gland). This temporary adrenergic hyperactivity is correlated with a significant depression of the thyroid economy resembling the nonthyroidal illness (NTT) syndrome in the rat, and suggest that the sympathetic nervous system may mediate thyroidal changes in NTI. In order to gain further insight into the thyroidal depression in the NT! syndrome, we studied the thyroidal norepinephrine (NE) turnover in turpentine oil (TURP)-induced NT syndrome and the role of the cervical ganglia (SCG) in the development of NΗ in the rat. TURP administration to sham operated rats induced a rapid and significant fall in plasma T4 and TSH levels, in the thyroidal response to exogenous TSH (ΗU) and in the thyroidal NE content compared to controls (sham + saline) (T4: 3.1 ± 0.3 vs. 5.1 ± 0.6 µg/dl, respectively, mean ± SE, p < 0.02; TSH: 1.4 ± 0.4 vs. 4.7 ± 1.4 ng/ml, respectively, p < 0.05; ΗU: 92 ± 14vs 201 ± 20 cpm µl thyroid/cpm·mg plasma (T/P ratio), respectively, p < 0.01; thyroidal NE: 680 ± 20 vs. 761 ± 29 pg/mg thyroid, respectively, p < 0.05). The thyroidal turnover rate of NE, however, was significantly increased in TURP-injected rats compared to controls (122 ± 13 vs. 86 ± 10 pg/mg/h, respectively, p < 0.05). TURP injection to chronic SCGx rats induced a similar fall in plasma TSH compared to controls (SCGx + saline) (1.3 ± 0.2 vs. 4.3 ± 1.1 ng/ml, respectively, p < 0.02); plasma T4 and TIU, however, did not change significantly (T4: 3.4 ± 0.4 vs. 3.7 ± 0.3 µg/dl, respectively, NS; ΗU: 172 ± 8 vs. 226 ± 27 T/P ratio, respectively, NS). Denervation of thyroid gland by sectioning of the external carotid nerve (ECNx) also blocked the fall in ΗU induced by TURP; on the other hand, a section of the internal carotid nerve (ICNx) (which does not innervate the thyroid gland) failed to prevent TURP effect on TIU (T/P ratio: sham + saline, 359 ± 58 vs. sham + TURP, 190 ± 23, p < 0.025; ECNx + saline, 266 ± 42 vs. ECNx + TURP, 274 ± 39, NS; ICNx + saline, 290 ± 57 vs. ICNx + TURP, 152 ± 29, p < 0.02). Our data suggest that (1) the NΠ is associated with an increase of the thyroidal NE turnover; (2) the SNS mediates the fall in plasma T4 and inTIU observed in NΠ syndrome through changes in the activity of the SCG, and (3) TSH fall in NΠ appears to be unrelated to SCG activity.

The present work studied the effects of epidermal growth factor (EGF) on the release of thyrotropin (TSH) and prolactin (PRL) from perifused pituitary glands of 200-gram male Wistar rats. Each pituitary gland, cut into halves, was placed in a chamber of a perifusion system connected to a peristaltic pump which conveyed the perifusion medium (Medium 199, pH 7.3, Gibco, USA) from a reservoir to a chamber at a flow rate of 100 µl/min. Each tightly closed chamber contained one pituitary gland and 600 µl medium and it was placed in a water bath at 37 ° C throughout the experiment. One milliliter samples of effluent were collected every 10 min for 60 min to obtain baseline values of TSH and PRL. Thereafter, TSH-releasing hormone (TRH) 10^–8M or EGF (10^–11, 10^–10, 10^–9 or 10^–8M) were added to individual chambers and the 10-min sampling of effluent continued for 60 min. EGF 10^–11M elicited no TSH response, but 10^–10 and 10^–9M doses induced significant increases in TSH secretion (p < 0.01) with a peak at 10 min after addition of EGF. In another experiment, EGF 10^–8M or TRH 10^–8M significantly elevated TSH secretion (p < 0.01). However, TRH, but not EGF, stimulated PRL secretion (p < 0.01). In the in vivo studies, the intravenous administration of EGF 10^–5 M or TRH 10^–5M both induced significant elevation of TSH release at 10 min after the injection (p < 0.02 for EGF and p < 0.01 for TRH). In summary, EGF stimulated TSH secretion from rat pituitary glands in vitro and in vivo, in a magnitude comparable to that of equimolar doses of TRH.

We have assessed the relative contribution of the thyroid hormones and noradrenaline (NA) on the calorigenic function of brown adipose tissue (BAT) as indicated by GDP binding and O2 consumption of BAT mitochondria. Male Wistar rats of 200 g body weight were made hypothyroid with 131I. Groups of animals were injected s.c., in divided doses, daily for 10 days, with thyroxine (2 micrograms/100 g body weight) or tri-iodothyronine (T3; 0.3 microgram/100 g body weight). Animals were used 7 days after bilateral or unilateral sympathetic nerve excision of BAT (Sx). Sham-operated rats were used as controls. In normal rats kept at 22 degrees C, GDP binding reached 94 +/- 24 pmol/mg protein; untreated hypothyroid rats had normal binding values whereas the T3-treated group showed an increased binding. Sx induced a sharp fall in the three groups (P < 0.01). After 24-h exposure to 4 degrees C GDP binding increased in normal rats to about 410% (P < 0.01) whereas binding failed to increase in response to cold in the untreated hypothyroid and the T3-treated groups. Sx reduced GDP binding in the three groups significantly (P < 0.01). The consumption of O2 by BAT mitochondria showed similar variations in response to Sx and to cold exposure as did GDP binding. The data indicated that, at room temperature, BAT calorigenesis can function without the thyroid hormones, though not without the catecholamines. The findings in rats exposed to cold showed that the lack of NA was significantly more effective than the lack of thyroid hormones in preventing the BAT hyperactive response. This does not negate an active role for T3 in BAT calorigenesis.