Adrenergic influence on progesterone metabolism and cyclicity in the rat ovary: autotransplantation and chemical sympathectomy.

Elimination of adrenergic nerve endings by chemical sympathectomy with 6-hydroxydopamine of normally cycling rats produced no differences in the weights of body, uterus, ovaries or adrenals, but suppressed significantly proestrus/estrus stages. Unilateral fully denervated (autotransplanted) ovaries showed the following changes in [¹4C]progesterone metabolism: the formation of 20α-hydroxy-4-pregnen-3-one increased, whereas 5α-pregnane-3α,20α- and 3ß,20α-diol, 3α- and 3ß-hydroxy-5α-pregnan-20-one, 20α-hydroxy-5α-pregnan-3-one, an unidentified metabolite Y and a group of hydrophobic metabolites decreased dramatically. Enzyme activities could not be restored with epinephrine. Sympathectomy changed the spectrum of [¹4C] progesterone metabolites in the same direction, but only at diestrus and metestrus. Autotransplantation suppressed 5α-reductase, 3α- and 3ß-hydroxysteroid dehydrogenase activities (-HSD) measured by the sum of all 5α-, 3α, and 3ß-metabolites, respectively. Sympathectomy suppressed significantly 5α-reductase and 3α-HSD at metestrus. 20α-HSD was not changed in any experiment. These studies provide evidence that 5α-reductase depends on adrenergic input in ovaries of rats at metestrus, a stage of nadir of gonadotropins. During the estrous cycle 5α-reductase may be a regulatory enzyme for progesterone metabolism and also influence estradiol biosynthesis.

[Steroid hormone transformation in the gonads and liver of aged rats]. / Steroidhormon-Transformation in Gonaden und Leber von Ratten im hohen Alter.

In order to study some aspects of the steroid hormone balance in old age the following organ functions of young and senescent male and female animals were investigated: 1) The capacity of testicular (45, 68-75 and 900 day-old animals) and ovarian tissue homogenates (29, 45, 66 and 900 day-old animals) to metabolically transform the sex hormone precursor, progesterone. 2) The capacity of liver slices (60-90 and 900 day-old animals) to generate a sex-specific metabolite pattern during incubation with testosterone. 3) The activities of some enzymes of steroid metabolism, which normally show sex differences in liver cell fractions (60-90 and 900 day-old animals). The testicular capacity of senescent animals to synthesize 17 alpha-hydroxyprogesterone, androstenedione and testosterone (main pathway of androgen biosynthesis) is drastically reduced compared to that of young adult rats; the reduction also extends to the production of highly polar C19O3- and C21O3-steroids. In contrast to these deficiencies, conversion of progesterone to 20 alpha-dihydroprogesterone increases in old age, whereas the generation of 5 alpha-hydrogenated compounds from testosterone and androstenedione remains unchanged. If the group of adolescent 45 day-old animals is also taken into consideration, then the biosynthetic sequence from progesterone to testosterone exhibits a biphasic developmental course. Production rates rise from low levels only to fall back to lower rates of synthesis in old age. In no age group can the production of oestrogens in measurable quantities be detected. However, 5 alpha-hydrogenated C19O2-steroid metabolites are detected, albeit only in prepuberal animals. After puberty only progesterone, 20 alpha-dihydroprogesterone and the 5 alpha-pregnane derivatives of these two steroids can be demonstrated. The pattern of the respective metabolites undergoes an age-dependent metabolite-specific development ending (900 day-old animals) with minimal yields of products (less than 21% of progesterone is converted). The production of hydroxylated metabolites (highly polar C21O3-steroid fraction) decreases very early in life (between day 29 and 45) to values indistinguishable from those of old animals. The sexually highly differentiated metabolite pattern of hepatic testosterone metabolism typical of young adult animals (60-90 day-old) is not prominent in old age. Both sexes exhibit a retarded testosterone turnover due to a decrease in the hydroxylating activity (males being more affected than females) and a deficiency of 5 alpha-hydrogenation (females only).(ABSTRACT TRUNCATED AT 400 WORDS)

Alterations in lymphocyte subpopulations in copper-deficient mice.

Analyses of cell surface determinants of splenocytes from copper-deficient C58 mice indicate alterations in lymphocyte subpopulation characteristics. Both the absolute number and the relative percentage of surface immunoglobulin-bearing (B) cells from copper-deficient mice were significantly greater than those from copper-supplemented controls. The relative percentage of Thy 1.2-positive (T) cells was decreased, and the decrease was most prominent within the Lyt 1-positive (helper) T-cell subset. The functional responsiveness of both B cells and T cells was decreased in copper deficiency.