Changes in the testis interstitium of Brown Norway rats with aging and effects of luteinizing and thyroid hormones on the aged testes in enhancing the steroidogenic potential.

We tested the possibility of using LH and thyroxine (T(4)) to restore the testicular steroidogenic ability in aged Brown Norway rats. Three-, 6-, 12- (n = 8 per group), and 18-mo-old (n = 32; 3M, 6M, 12M, and 18M, respectively) rats were used. The 18M rats were divided into four groups (n = 8 per group) and implanted subdermally with Alzet mini-osmotic pumps containing saline (control), LH (24 microg/day), T(4) (5 microg/day), and LH+T(4) (24+5 microg/day), respectively, for 4 wk (to 19 mo [19M] of age). Testis volume and absolute volumes of many testicular components were unchanged with advancing age and treatments, except for the blood vessels (occasional thickening), lymphatic space (increased), and Leydig cells (decreased with age but increased to the 3M level with LH and to the 12M level with both T(4) and LH+T(4), respectively). The number of Leydig and connective tissue cells per testis was unchanged with aging and treatments. The number of macrophages was significantly higher in treated rats. The average volume of a Leydig cell was significantly decreased in 12M and 19M control rats. However, LH and LH+T(4) restored it to the 3M level, and T(4) restored to the 12M level. The steroidogenic ability of Leydig cells in vitro decreased when aging from the 3M to the 19M level, LH and T(4) enhanced it to the 12M level, and LH+T(4) raised it to the 3M level. Serum LH was unchanged from 3M to 12M rats, significantly reduced in 19M control rats, and raised above the 3M values with both LH and LH+T(4) treatment and above the 19M (control) values with T(4) treatment; the latter values were lower than the 3M level. Serum T(4) and tri-iodothyronine (T(3)) were highest in 3M and 6M rats and declined in 12M and 19M control rats; the latter group had the lowest levels. In all treated groups, T(4) and T(3) levels were significantly above those of 19M control rats but were lower than those of 3M through 12M rats. Serum testosterone was unchanged from 3M to 12M rats but was reduced in 19M control rats. Both LH and T(4) significantly raised these values above the 19M control levels, but they were still lower than the 3M through 12M levels. Additionally, LH+T(4) significantly raised the serum testosterone levels to those of 12M rats, but these values were significantly lower than those of 3M and 6M rats. These findings show that with 24+5-microg dose of LH+T(4) per day for 4 wk, a 100% recovery of the average volume of a Leydig cell and its steroidogenic ability in vitro and a 73% and 300% restoration of serum testosterone levels compared to 3M and 19M control rats, respectively, could be achieved in aged Brown Norway rats. A 100% reversibility (compared to 3M rats) in serum testosterone levels appears to be possible with adjustments in the LH and T(4) doses in the LH+T(4) treatment.