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Because the submandibular salivary glands of male mice are rich in growth factors such as epidermal growth factor and nerve growth factor, and because there are sporadic reports of sialadenectomized mice showing growth retardation and endocrine abnormalities, we studied oxidative metabolism and fertility after submandibular sialadenectomy. Despite similar intake of food, male mice (n = 60) deprived of submandibular saliva, either by duct ligation or gland excision, initially weighed 12-13% less than the sham controls and had a slower rate of growth (P less than 0.001). After 5 mo, mice with duct ligation caught up with the sham-operated mice, but the differences compared with submandibular-sialadenectomized mice were still apparent at 32 wk (P less than 0.001). The mean respiratory quotient of submandibular-sialadenectomized and duct-ligated mice was 0.71 instead of 0.88 as in the shams at 10, 20, and 30 wk after operation (P less than 0.01). No effect on fecundity was observed in either male or female mice following submandibular sialadenectomy.

An implantable drug-delivery and venous sampling device is described that is constructed from a polyvinyl chloride catheter and a rubber intravenous catheter plug coated with Silastic. The implant was used for repeated venous sampling and for both administration of parenteral solutions and injections into the right colon of the rat for periods to 1 mo.

Induction of metallothionein mRNA was investigated in organs of mice receiving oral zinc and cadmium. The low molecular weight, heat stability, and 30% cysteine content of metallothionein facilitated its detection in cell-free translation products analyzed by Sephadex G-50 chromatography and by gel electrophoresis. Native and heat-denatured [35S]cysteine-labeled polypeptides directed by poly(A)+ mRNA from organs of mice exposed orally to 3 mg CdCl2 or 15 mg ZnCl2 were compared with those of control mice. Although parenteral administration of CdCl2 (30 micrograms) did not elicit a measurable metallothionein mRNA accumulation in gut, oral administration of this metal induced intestinal metallothionein mRNA to high levels; translatable metallothionein mRNA was not detected in control organs. Five hours after oral CD or Zn, metallothionein constituted 12-17% of [35S]cysteine directed into protein by gut mRNA, and metallothionein mRNA was induced to similar levels in liver, kidney, and spleen of the same mice. After oral Zn, metallothionein mRNA levels in proximal jejunum were twice those in other regions of intestine. Metallothionein mRNA accumulates rapidly in small bowel after oral Zn and Cd; simultaneous induction in other mouse organs indicates a systemic response.

To help determine the roles of lost renal mass and lost excretory ability in producing renoprival hypertrophy, observations were made in otherwise normal rats cross-circulated for 24 h with rats prepared in one of the following ways: bilateral nephrectomy, bilateral ureteral ligation, or bilateral nephrectomy with 24 h of uremia. Bilateral nephrectomy produced parabiotic increases in renal mass and in the average cellular concentration of RNA: bilateral ureteral ligation did not. Uremia did not potentiate the effects of bilateral nephrectomy. Lost mass is the determinant of compensatory renal hypertrophy.

Ribosomal synthesis was studied at the transcriptional and translational levels to investigate the mechanisms of ribosome accretion during compensatory renal hypertrophy. As measured by in vitro transcriptional runoff comparisons 6-48 h after surgery, nuclei from the kidney remaining after contralateral nephrectomy show an increase of up to 150% in the rate of synthesis of ribosomal precursor RNA. The rate of rDNA transcription is 40-50% greater than control values as early as 6 h after nephrectomy; by 48 h, the rate returns to normal. In contrast to the stimulated transcription of rDNA and accretion of rRNA, the steady-state levels and the cytoplasmic distribution of ribosomal protein mRNAs S16 and L10 remain unchanged during induced renal growth. Thus coordinate production of adequate protein for increased assembly of ribosomes during induced renal growth appears to be accomplished by increasingly efficient translation of existing ribosomal protein mRNAs or by post-translational stabilization of ribosomal proteins. The rate of rDNA transcription may be regulated by accelerating the transcription of already functioning genes or, more likely, by recruiting transcription units that are transcriptionally inactive in the normal kidney.

To examine the regulatory role of mRNA in compensatory renal hypertrophy, the accumulation and decay of [3H]orotic acid in poly(A)-containing mRNA in mouse kidney was analyzed after unilateral nephrectomy during the period of maximal rRNA accretion. The distribution of radioactivity between newly synthesized poly(A)-containing and poly(A)-lacing polysomal RNA was altered, but no differences in mRNA half-life were observed in growth compared with effects of sham nephrectomy. Radioactivity in polysomal polyadenylated RNA was diminished by approximately 25% during growth where mice were labeled after nephrectomy, but if mice were labeled 18 h before operation, no difference was noted. Thus, accumulation of newly synthesized poly(A)-containing mRNA relative to RNAs that lack poly(A) is changed early in the course of renal hypertrophy. This noncoordinate regulation may represent a control mechanism effective early in induced cell growth involving mRNAs that lack poly(A).