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R L Stouffer

Publications and source records attributed to R L Stouffer.

At least 127 records · Page 7Linked to original sources
PubMed1984

Changes in available gonadotropin receptors in the corpus luteum of the rhesus monkey during simulated early pregnancy.

Stimulation of the primate corpus luteum (CL) by endogenous CG in early pregnancy or by exogenous human CG (hCG) in simulated early pregnancy, is transient, despite continued exposure to rising concentrations of CG. The objective of this study was to determine if the transitory response of the CL to CG is related to changes in gonadotropin receptors. Numbers and affinities of available LH/CG binding sites were characterized in the CL of rhesus monkeys (n = 27) during prolonged CG exposure in simulated early pregnancy, and the temporal relationship between changes in receptor parameters and in luteal function was examined. Administration of hCG increased progesterone concentrations above pretreatment levels within 9 h (2.2 +/- 0.8 vs. 7.6 +/- 1.1 ng/ml, mean +/- SE, P less than 0.05); the relative increase (345% of control) in serum progesterone was more profound than that of available hCG binding sites (135%, P greater than 0.05) or luteal weight (128%, P greater than 0.05) over this interval. Receptor affinities for hCG remained comparable to pretreatment values (Kd = 1.1 +/- 0.2 X 10(-10) M) throughout this 9-h period. A significant diminution in available hCG receptors occurred between 9 h (12.7 +/- 2.1 fmol/mg tissue) and 3 days (7.4 +/- 1.5 fmol/mg tissue) of hCG treatment (P less than 0.05). The loss of available CG receptors preceded a significant decline in serum progesterone concentrations. Serum progesterone decreased by 6 days (4.0 +/- 0.6 ng/ml, P less than 0.05) of hCG treatment, as did receptor affinity for hCG (Kd = 4.7 +/- 0.9 X 10(-10) M, P less than 0.05). Numbers and affinities of available receptors for hCG and serum progesterone concentrations fell before any decrease in luteal weight. Binding capacities and receptor affinities for human LH were comparable to those for hCG throughout simulated early pregnancy. In conclusion, the population of available LH/CG receptors in the macaque CL is maintained, or perhaps modestly increased, amidst dramatic stimulation of luteal function during early CG exposure. The subsequent diminution of number and affinity of available LH/CG receptors during prolonged exposure to CG in early pregnancy may compromise CL function and thus participate in the establishment of the transient nature of the luteal response to CG.

Animals↗
PubMed1984

Follicular fluid treatment during the follicular versus luteal phase of the menstrual cycle: effects on corpus luteum function.

Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys at the time of menses impairs the subsequent function of the corpus luteum of the menstrual cycle. The following studies were performed: 1) to characterize the luteal phase defect induced by pFF treatment at menses, and 2) to determine whether pFF treatment in the luteal phase alters corpus luteum function. Adult, female rhesus monkeys were injected sc for 3 days with pFF (10, 5, and 5 ml) beginning on day 1 (n = 5) or day 18 (n = 4) of the menstrual cycle. Femoral venous blood was collected daily throughout the treatment cycle and during the posttreatment cycle of day 18 to 20-treated monkeys. Serum LH, FSH, 17 beta-estradiol (E2), and progesterone (P) were measured by RIA. After pFF treatment on days 1-3, FSH and E2 levels in the early follicular phase were less (P less than 0.05) than those of control cycles (n = 7). Serum LH was not suppressed by pFF treatment. Moreover, the preovulatory rise in circulating E2 and the amplitude of the LH/FSH surge were similar in control and pFF-treated monkeys. Although timely midcycle gonadotropin surges occurred in four of five pFF-treated monkeys, serum P was markedly reduced (P less than 0.05) during the first half of the luteal phase. Circulating P increased to control levels during the late luteal phase before normal onset of menses 16.3 +/- 1.0 (SE) days after the LH surge. Treatment with pFF on days 18-20 of the cycle reduced the levels of circulating FSH, but serum LH, E2, P, and the length of the luteal phase remained comparable to control cycles. Moreover, the hormonal patterns and the length of the follicular and luteal phases in the posttreatment cycle indicated normal ovarian function. Thus, pFF treatment at menses results in an aberrant ovarian cycle characterized by an insufficient, rather than short, luteal phase. Whereas pFF treatment in the early follicular phase vitiates development of the dominant follicle and the related corpus luteum, similar treatment at midluteal phase does not suppress concurrent luteal function or subsequent folliculogenesis.

Animals↗
PubMed1984

Investigation of binding sites for follicle-stimulating hormone and chorionic gonadotropin in human ovarian cancers.

The binding of FSH and hCG to ovarian tumor biopsies from 31 women was analyzed to determine whether ovarian cancers contain receptors for gonadotropic hormones. For comparative purposes, gonadotropin binding to receptor-positive control tissues was also assessed. Specific binding was defined as [125I]hFSH and [125I]hCG binding prevented by coincubation of tissue samples with an excess of unlabeled gonadotropin. Various types of epithelium-derived tumors (serous, mucinous, endometrioid, and undifferentiated; n = 29) had low levels of specific FSH and hCG binding (less than 15% of receptor-positive control tissues) which were not dependent on tissue concentration and not saturable. A germ cell tumor had similar binding characteristics. In contrast, specific FSH binding to a granulosa cell-theca cell (GC-TC) tumor was directly proportional to tissue concentration, and binding was maximal in the presence of 100 ng/ml [125I]FSH. Scatchard analyses of FSH binding yielded a linear plot. Although the FSH-binding capacity of the GC-TC tumor (6.3 fmol/mg) exceeded that of control tissues, their binding affinities (Kd = 1.4 X 10(-9)M) were similar. Specific hCG binding to the GC-TC tumor was low and not dependent on tissue concentration. We conclude that the specific binding of FSH to the GC-TC tumor was characteristic of the interaction of gonadotropin with receptors in target tissues. However, the low level of FSH and hCG binding to tumors of epithelial origin did not represent gonadotropin-receptor binding. Thus, the common ovarian tumors of epithelial origin may not respond directly to gonadotropin, but malignancies of sex cord-stromal origin, such as GC-TC tumors, could be modulated by FSH.

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PubMed1982

In vitro effects of ethanol on primate luteal membranes: exposure of additional gonadotropin receptor sites.

The presence of 0.8-8.0% (vol/vol) ethanol increased the specific binding of [125I]human luteinizing hormone (hLH) to membrane particulate fractions prepared from the rhesus monkey corpus luteum in a dose-dependent manner. Ethanol increased the number of available gonadotropin binding sites without altering their affinity for LH. These results suggest that (1) there are additional gonadotropin receptors in the macaque corpus luteum which are not detected by conventional in vitro techniques, and (2) ethanol exposes receptors previously unavailable for hormone interaction.

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PubMed1980

Progesterone production by luteal cells isolated from cynomolgus monkeys: effects of gonadotropin and prolactin during acute incubation and cell culture.

Corpus luteum function in cynomolgus monkeys (Macaca fascicularis) during the menstrual cycle and immediately following parturition was evaluated through in vitro studies on progesterone production by dispersed luteal cells in the presence and absence of human chorionic gonadotropin (hCG) or human prolactin (hPRL). Luteal cells isolated between days 17-20 of the menstrual cycle secreted progesterone (P) during short-term incubation (21.6 +/- 1.2 ngP/ml/5 X 10(4) cells/3 hr, X +/- S.E., n = 7) and responded to the addition of 1-100 ng hCG with a significant (p less than 0.05) increase in P secretion. Cells removed the day of delivery secreted large, but variable (27.9-222 ng/ml, n = 4) amounts of P during short-term incubation. Moreover, hCG (100 ng/ml) stimulation of P production by cells at delivery (176 +/- 19% of control) was less than that of cells from the cycle of (336 +/- 65%). The presence of hPRL (2.5-5000 ng/ml) failed to influence P secretion by luteal cells during short-term incubation in the presence or absence of hCG. P production by luteal cells obtained following delivery declined markedly during 8 days of culture in Ham's F10 medium: 10% fetal calf serum. Continual exposure to 100 ng/ml of hCG or hPRL failed to influence P secretion through Day 2 of culture. Thereafter hCG progressively enhanced (p less than 0.05) P secretion to 613% of control levels at Day 8 of culture. In contrast, hPRL significantly increased P secretion (163% of control levels, p less than 0.05) between Day 2-4 of culture, but the stimulatory effect diminished thereafter. The data indicate that dispersed luteal cells from the cynomolgus monkey provide a suitable model for in vitro studies on the primate corpus luteum during the menstrual cycle, pregnancy, and the puerperium, including further investigation of the possible roles of gonadotropin and PRL in the regulation of luteal function in primates.

Animals↗
PubMed1980

Induction of luteal phase defects in rhesus monkeys by follicular fluid administration at the onset of the menstrual cycle.

Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys on days 1-3 of the menstrual cycle suppressed serum FSH, but not LH, during the early follicular phase. Although timely midcycle gonadotropin surges occurred in 5 of 6 pFF-treated monkeys, the preovulatory rise in serum estradiol was markedly diminished and serum progesterone (P) levels were subnormal at midluteal phase. The wet weight of the corpus luteum excised from pFF-treated monkeys at midluteal phase was less than that from controls. Moreover, both basal and gonadotropin (hCG)-sensitive P production by short-term suspensions of luteal cells from pFF-treated monkeys was significantly less than that by control cells. These findings provide direct support for the concept that FSH-dependent events during the early follicular phase are important determinants of the subsequent function of the corpus luteum of the menstrual cycle. Since pFF-induced luteal dysfunction was strikingly similar to spontaneous luteal phase defects found in monkeys and women, this primate model permits study of the mechanism(s) whereby FSH deficiency during recruitment and selection of the dominant follicle portends defective luteal function and infertility in women.

Animals↗
PubMed1977

Serum estradiol and progesterone during pregnancy and the status of the corpus luteum at delivery in cynomolgus monkeys (Macaca fascicularis).

Levels of estradiol and progesterone in peripheral serum of seven cynomolgus monkeys (Macaca fascicularis) were measured from about the 30th day of pregnancy until parturition. Although the pattern of each steroid in circulation differed somewhat from the respective patterns in rhesus monkeys (Macaca mulatta), there were basic similarities. On the day of delivery, the corpus luteum was excised and in vitro incubation of dispersed luteal cells was performed. Isolated luteal cells produced progesterone under control conditions and responded to the addition of HCG with enhanced steroidogenesis. Accordingly, "rejuvenation" of the corpus luteum may occur during advanced gestation in cynomolgus monkeys. These findings, along with establishing the efficacy of the Subhuman Primate Pregnancy Test kit to diagnose pregnancy in this macaque, extend previous evidence for utility of cynomolgus monkeys as a primate model for study of steroid hormones in pregnancy.

Animals↗
PubMed1977

Corpus luteum function during the early postpartum interval in lactating rhesus monkeys: in vivo and in vitro response to exogenous gonadotropin.

The response of the postpartum corpus luteum to exogenous gonadotropin was studied in 12 lactating rhesus monkeys given daily injections of either human chorionic gonadotropin (HCG, n = 6) or saline (control, n = 6) for 4 days immediately following parturition. Peripheral blood samples were collected daily. On the 5th day postpartum, luteectomy was performed progesterone production by dispersed luteal cells was examined. Whereas progesterone in the peripheral circulation of control monkeys progressively declined between days 1 and 5 postpartum, progesterone levels increased significantly (p less than 0.025) with the onset of HCG treatment and remained significantly (p less than 0.025) elevated above the controls throughout the period of HCG treatment. However, despite the daily administration of HCG, circulating progesterone levels declined (p less than 0.05) between days 3 and 5 postpartum. The weight of the corpus luteum excised from HCG-treated macaques was significantly (p less than 0.005) greater than that of the controls. Dispersed cells from corpora lutea of saline-treated monkeys produced progesterone in vitro under control conditions (nutrient medium alone) and responded to the addition of high (100 ng/ml), but not low (1 ng/ml), levels of HCG with increased steroidogenesis. Although luteal cells from HCG-treated macaques tended to produce more progesterone in vitro than cells from control monkeys, they also exhibited a 50-fold reduction in sensitivity to HCG in vitro. These data suggest that the corpus luteum of lactating postpartum rhesus monkeys exhibited steroidogenic function which was stimulated by exogenous gonadotropin. However, prolonged exposure of the corpus luteum to high levels of exogenous gonadotropin appeared to produce a state of refractoriness to additional gonadotropic stimuli.

Animals↗
PubMed1977

Gonadotropin-sensitive progesterone production by rhesus monkey luteal cells in vitro: a function of age of the corpus luteum during the menstrual cycle.

Progesterone production in vitro, in the presence and absence of exogenous gonadotropin, was examined in suspensions of luteal cells, isolated by collagenase digestion of rhesus monkeys corpus luteum at various stages of the menstrual cycle. Cells isolated during mid-luteal phase (days 15-19) of the cycle secreted progesterone for up to 6 h in vitro. Mid-luteal phase cells were responsive to physiologic concentrations of human chorionic gonadotropin (hCG), with progesterone production significantly (P less than 0.05) enhanced by as little as 0.1 ng hCG/ml. Maximal stimulation was obtained with 100 ng hCG/ml. Both macaque chorionic gonadotropin (mCG) and human luteinizing hormone (hLH) significantly (P less than 0.01) increased progesterone production, while human follicle stimulating hormone (hFSH) did not. Under control conditions, in the presence of nutrient medium alone (no exogenous gonadotropin), the progesterone synthetic activity of mid-luteal phase cells was significantly (P less than 0.01) greater than that of cells from late luteal phase (days 22-28) of the cycle. Moreover, progesterone production by mid-luteal phase cells was consistently stimulated (P less than 0.01) by the presence of 100 ng hCG/ml, whereas late luteal phase cells were less sensitive or unresponsive to exogenous gonadotropin. The progesterone synthetic activity of luteal cells in vitro correlated positively with both the wet weight of the excised corpus luteum (r = 0.82, P less than 0.01) and the peripheral serum progesterone concentration immediately preceding luteectomy (r = 0.66, P less than 0.01). These findings suggest that freshly isolated luteal cells reflect the functional capability of the corpus luteum in vivo. It is apparent that the age of the rhesus monkey corpus luteum of the non-fertile menstrual cycle is an important factor governing luteal cell progesterone synthetic capability and luteal cell responsiveness to gonadotropin in vitro.

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