Neonatal androgenization in the male rat: evidence for central and peripheral defects.

Studies were conducted to evaluate the development of the reproductive axis of the male rat androgenized with low-dose, chronic exposure to testosterone. Male rats were implanted with a testosterone-containing Silastic capsule on the day of birth. Capsules were left in the animals for 10 days, 20 days or permanently. Results indicate that in androgenized (A) rats, the weights of the testes (T), ventral prostate (VP) and seminal vesicles (SV) were significantly depressed in most age groups when compared to controls (C), regardless of the duration of capsule retention. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (Prl) levels were not altered in adult (85 and 100 days old) A rats, but FSH and LH did show significant changes in young animals with testosterone-filled capsules. The efficacy of testosterone in promoting VP and SV growth, and increasing protein/DNA ratios in castrated A rats was significantly reduced compared to C rats, but it was increased with respect to suppression of LH secretion. Results suggest that a low, chronically administered dose of testosterone during the early neonatal period can produce permanent changes in the reproductive axis of the male rat and that these changes may be both central (hypothalamo-hypophysial) and peripheral (testes and accessory structures).

Chronic pulmonary inflammation modulates the fate of proteins administered by the respiratory tract. Organ distribution of radiolabeled proteins.

In a previous report we found that, following intrapulmonary administration of radiolabeled albumin, blood concentrations were higher in rabbits with BCG-induced chronic pulmonary inflammation (CPI) than in normal rabbits. The present study demonstrates that this increased blood concentration was not the result of decreased blood clearance by other organs, indicating that increased absorption through the respiratory tract occurred in the inflamed lungs. In addition, rabbits with BCG-induced CPI had larger hilar lymph nodes and larger concentrations of radioactivity in the hilar lymph nodes, suggesting that the pulmonary lymphatics are a route of increased absorption through inflamed lungs.

Enhancement of systemic immune response by immunization into chronically inflamed lungs.

Intrapulmonary instillation of proteins into rabbit lungs with BCG-induced granulomatous inflammation results in greater transport of these molecules into the blood, and the primary route is probably the pulmonary lymphatics. In addition, rabbits with inflamed lungs develop a more potent systemic immune response when exposed to soluble antigens as an aerosol. The current study was done to further study the mechanisms of this phenomenon using the Jerne plaque technique. Intrapulmonary immunization with soluble antigens (solubilized SRBCs and HSA) resulted in a greater PFC response to both antigens when the lungs exhibited BCG-induced granulomatous inflammation. A previous study demonstrated that more antigen administered intratracheally was found in the HLNs when the lungs displayed granulomatous inflammation. However, in the present study, we did not observe an enhanced PFC response in HLN cells when antigens were introduced into inflamed lungs. When rabbits with BCG-inflamed lungs were immunized i.v., they did not develop an enhanced PFC response in the spleen. Immunization into the respiratory tract of normal rabbits with large doses (300 micrograms) of soluble antigens also resulted in a substantial PFC response in the spleen that was quantitatively greater than that induced by the same i.v. dose. These data indicate that (1) administration of antigens into inflamed lung results in an enhanced systemic immune response, (2) although larger quantities of soluble antigens administered by the pulmonary route accumulate in the HLN when lungs are inflamed, cells from this tissue do not exhibit an enhanced PFC response, and (3) large doses of soluble antigens instilled into normal lungs induce a greater systemic immune response that the same doses administered i.v. This study further demonstrates the importance of pulmonary inflammation and the immune response to inhaled antigens and provides insight as to how individuals with chronic inflammatory lung disease can react in an augmented fashion to environmental antigens.

Effect of passive immunization on absorption of antigen through the respiratory tract.

Isolated perfused rabbit lungs were insufflated with 125I-labeled bovine serum albumin (125I-BSA) and the accumulation of radioactive BSA and its breakdown products was measured in the blood. The addition of anti-BSA serum to the blood caused a 4- to 6-fold reduction in the amount of 125I-BSA which appeared in the blood following the insufflation. To determine whether this reduction was the result of inhibition of absorption or the reuptake of 125I-BSA antigen-antibody complexes formed in the blood, we infused the 125I-BSA into the anti-BSA containing blood perfusing the lungs. Virtually none of the radioactivity was taken up by the lungs, indicating that the reduced blood levels following insufflation were the result of reduced absorption through the lung resulting from antigen-antibody interaction within the alveolocapillary membrane or the bronchoalveolar secretions.

Patterns of pituitary and gonadal hormone secretion during a 24 hour period in the male rat.

PIP: Levels of serum concentrations of luteinizing hormone (LH) total androgens, prolactin, follicle stimulating hormone (FSH), TSH, and growth hormone (GH) throughout the 24-hour period in male rats were determined and the temporal relationships between the maximum or minimum secretory periods of the various hormones. Animals were maintained on a schedule of 14 hours light and 10 hours dark (light 0500-1900 hours). Animals were killed at regular intervals throughout the 24-hour period by decapitation. Serum concentrations of LH and androgens were found to vary significantly (p less than .05 and p less than .01 respectively) during the day. The nadir was found for both at 0530 hours. Peaks were absent for both hormones. Serum prolactin exhibited distinct diurnal variations (p less than .001). A pronounced surge was seen at 0530 hours. Within 3 hours of this peak prolactin subsides and androgen and LH values rise significantly. A distinct diurnal variation was recorded for FSH (p less than .001) with the peak values occurring at 0300 hours. This increase in FSH was accompanied by an increase in prolactin and a decrease in total androgens. Large variations in individual TSH values were recorded at most of the killing periods resulting in the conclusion that TSH was without diurnal variation. GH also was without diurnal variation.^ieng