Interspecific and intraspecific competition as causes of direct and delayed density dependence in a fluctuating vole population.

A 3- to 5-year cycle of vole abundances is a characteristic phenomenon in the ecology of northern regions, and their explanation stands as a central theoretical challenge in population ecology. Although many species of voles usually coexist and are in severe competition for food and breeding space, the role of interspecific competition in vole cycles has never been evaluated statistically. After studying community effects on the population dynamics of the gray-sided vole (Clethrionomys rufocanus) in the subarctic birch forest at Kilpisjärvi, Finland, we report statistical results showing that both interspecific and intraspecific effects are important in the direct year-to-year density dependence. However, interspecific effects are not detectable in the 2-year delayed density dependence that is crucial for generating the characteristic cycles. Furthermore, we show that most of the competition takes place during the winter. The results are evaluated against two models of community dynamics. One assumes that the delayed effects are caused by an interaction with a specialist predator, and the other assumes that they are caused by overgrazing food plants. These statistical results show that vole cycles may be generated by a species-specific trophic interaction. The results also suggest that the gray-sided vole may be the focal species in the birch-forest community, as field voles may be in the taiga and as lemmings may be on the tundra.

Analysis of differential gene regulation in adequate versus inadequate secretory-phase endometrial complementary deoxyribonucleic acid populations from the rhesus monkey.

The ability to create artificial menstrual cycles in the rhesus monkey provides a model for studies on the regulation of genes and gene networks by estradiol or progesterone (P) in the primate endometrium. This model allowed us to create both a normal level of secretory phase P or an inadequate level of secretory phase P, i.e. endometria that cannot support implantation. The objective of our present study focused on PCR analyses of genes for several factors that are believed to be important in the proper maturation of the endometrium. Complementary DNA (cDNA) populations were prepared from endometria harvested on day 13 (peak E level), days 21-23 of an adequate secretory phase (PcDNA) and days 21-23 of an inadequate secretory phase (IcDNA). Although placental protein 14, leukemia inhibitory factor and 17-beta hydroxysteroid dehydrogenase displayed highly upregulated levels in PcDNA (P-activated genes), there was little or no up-regulation in IcDNA. Transforming growth factor-beta 2 and its receptor and insulin growth factor-I and its receptor were up-regulated in PcDNA, whereas little or no expression was observed in IcDNA. Regulators of the cell cycle and transcription, such as retinoblastoma, c-fos, and c-jun genes, were also greatly underexpressed in IcDNA compared with PcDNA. Interestingly, one gene that we studied, keratinocyte growth factor, that was up-regulated by P (peak E levels vs. PcDNA) was more highly expressed in IcDNA. This latter result suggests that low levels of circulating P are sufficient for expression of this gene, whereas high sustained P levels result in an autologous down-regulation. These data show that the regulation of genes that may play pivotal roles in endometrial maturation are differentially expressed in IcDNA vs. PcDNA and may, in part, characterize improper endometrial maturation.

Dehydroepiandrosterone metabolism in the female rhesus monkey: oral versus intravenous administration.

Because of the biologic effects on a variety of end points reported for dehydroepiandrosterone (DHA) and its sulfate (DHAS) after oral administration, we studied the metabolism of DHA in six female rhesus monkeys after oral and after intravenous administration. We administered [4-14C]DHA p.o. and [7-3H]DHA i.v. simultaneously, drawing blood samples at increasingly longer intervals for 24 h. The mean +/- SE metabolic clearance rate of the intravenous DHA was 404 +/- 49 L/day. The mean metabolic clearance rate was 2,601 +/- 261 L/day after oral administration, and the calculated absorption was 16.3 +/- 2.5%. There was rapid conversion of p.o. DHA to DHAS, as the conversion ratio of the orally administered DHA measured in the blood as [4-14C]DHAS was 63.3 +/- 13.6, whereas the conversion ratio of intravenously administered DHA to DHAS was 9.3 +/- 2.0. Small amounts of DHA were measured in the blood as testosterone and androstenedione after both forms of administration. We conclude that there is marked metabolism in splanchnic tissue of orally administered DHA to DHAS prior to its entry into the bloodstream, and the absorption of DHA itself is minimal when administered by mouth to the rhesus monkey.

The metabolism of estrone sulfate in the female rhesus monkey.

In order to study the metabolism of estrone sulfate in the adult female rhesus monkey, we gave four monkeys a pulse injection of [3H]estrone sulfate and obtained blood samples at 15, 30, 60, 120, 300, and 1,440 minutes after the pulse. All blood samples were analyzed for [3H]estrone sulfate. The mean +/- SE for the initial volume of distribution was 4.6 +/- 0.9 L. The mean metabolic clearance rate (MCR) was 42.0 +/- 2.9 L/day. In addition, 2 monkeys were infused for 240 minutes with [3H]estrone sulfate and 5 monkeys were infused for 240 minutes with [3H]estrone sulfate/[14C]estrone. Three blood samples were obtained during the last hour of the infusions and analyzed for radioactivity as estrone sulfate, estrone, and estradiol, and MCRs, conversion ratios, and [rho]BB values were calculated. The mean +/- SE for the MCR was 67.5 +/- 8.3 L/day, and for the conversion ratio, estradiol to estrone sulfate was 0.054 +/- 0.016. The mean [rho]BB value for estrone sulfate conversion to estrone was 43.6 +/- 3.4% and for estrone conversion to estrone sulfate was 33.5 +/- 6.6%. Thus estrone sulfate is cleared slowly and is converted to both estrone and estradiol. The hydrolysis of estrone sulfate to estrone is not significantly different than the conversion of estrone to estrone sulfate.

The effects of ovariectomy and progesterone on peripheral aromatization in the female rhesus monkey.

We investigated the acute effects of surgery, i.e. ovariectomy, the long-term effects of ovariectomy, and the effects of progesterone on the peripheral aromatization of androstenedione in rhesus monkeys (Macaca mulatta). For the acute effects of surgery, 7 rhesus monkeys were given a pulse of [3H]androstenedione/[14C]estrone 2 weeks before and immediately after ovariectomy. In each case all urine was collected for 4 days and analyzed for radioactivity as estrone glucuronide and the peripheral aromatization calculated from the isotope ratios. Similarly, 5 monkeys were studied before and 18 months after ovariectomy. The acute effects of surgery resulted in a significant decrease in the peripheral aromatization of androstenedione to estrone from a mean +/- SE of 0.94 +/- 0.26 to 0.61 +/- 0.19%, P = 0.0452. Conversely, the long-term effects of ovariectomy resulted in a significant increase in peripheral aromatization from 0.38 +/- 0.06 to 0.67 +/- 0.12%, P = 0.0207. In 7 monkeys the peripheral aromatization was measured before and 10 days after the administration of progesterone, 100 mg in oil. There was no difference in peripheral aromatization before, 0.62 +/- 0.04% and after progesterone, 0.58 +/- 0.05%, P = 0.10. We conclude that the acute stress of ovariectomy, or possibly the loss of ovarian aromatizing tissue, results in a decline in peripheral aromatization, but ovariectomy will have the long-term effect of an increase in aromatization, and that the presence or absence of progesterone does not play a role.

Estradiol, progesterone, and sex hormone-binding globulin in female rhesus monkeys (Macaca mulatta).

We measured the concentrations of estradiol, progesterone, and the sex hormone-binding globulin capacity (rhSHBG) in serum of female rhesus monkeys (Macaca mulatta). Although the serum rhSHBG capacity was altered by the removal of ovarian hormones, presumably estradiol, acute changes in serum estradiol and progesterone did not influence SHBG capacity. There appears to be a relatively low threshold for the effect of estradiol on rhSHBG capacity. The threshold must be present for a finite length of time to have that effect.

Progesterone regulation of endometrial estrogen receptor and cell proliferation during the late proliferative and secretory phase in artificial menstrual cycles in the rhesus monkey.

Progesterone (P) down-regulation of uterine estradiol (E) receptor (ER) appears to be a general mechanism by which P modulates E action in the uterus. Our present studies focus on the regulation of ER by P during the changeover from E to P dominance during artificial menstrual cycles in the rhesus monkey. Because of differential cell-type response and the cellular zonation of the primate uterus, we used immunohistochemical analysis in addition to biochemical assays to study the regulation of ER by P. Ki-67 immunoreactivity was used as an index of endometrial proliferation. We performed our analyses on Days 13 (peak of E), 14 (declining E and rising P), 17 (basal E and rising P), and 21 (basal E and peak P). ER immunoreactivity was present throughout the endometrium in luminal and glandular epithelia and stromal fibroblasts on Day 13. As E was withdrawn and P rose on Day 14 there were few distinct changes in ER staining in stromal and epithelial cells. On Day 17, immunoreactive staining showed a distinct reduction for stromal cells in all zones. Although luminal epithelial cells showed a decrease in immunoreactivity on Day 17, zones II, III, and IV retained positive staining for ER in glandular epithelia. ER staining in stromal cells on Day 21 was similar to the pattern observed on Day 17, whereas epithelial cells in zones I, II, and III showed a reduction in staining. Glandular epithelia in zone IV maintained strong positive staining for ER on Day 21.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolism of human sex hormone-binding globulin in the rhesus monkey.

The metabolism of human sex hormone-binding globulin (hSHBG) was studied in eight female rhesus monkeys (Macaca mulatta) after the pulse injection of [125I]-hSHBG. hSHBG was iodinated with 125I using a chloramine T technique, and the [125I]-hSHBG was separated from other constituents by molecular sieve chromatography with a Sephadex G-25 column. The [125I]-hSHBG was administered intravenously as a pulse in 2 ml of phosphate buffer, pH 7.4, to each of eight rhesus monkeys. Blood samples (2.0 ml) were obtained at 2, 4, 6, 8, 24, 30, 45, and 54 hr after the injection. The glycoproteins were precipitated with concanavalin A-Sepharose, and the radioactivity was measured. The concentration of radioactivity as fraction of dose/ml of serum was plotted on a semilog scale against time. The disappearance of radioactivity could be expressed best as the sum of two exponentials, with a mean +/- SE t1/2 of 2.5 +/- 0.4 and 33.1 +/- 3.7 hr, respectively. The initial volume of distribution was 461 +/- 78 ml and the metabolic clearance rate was 559 +/- 66 ml/day. The very low clearance rate and prolonged t1/2 are compatible with a relative stability in the circulating mass of SHBG. Rapid changes in concentration of SHBG could be due to changes in serum volume, reversible changes in tissue distribution of SHBG, or the secretion of variable forms of desialylated SHBG.