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Biomedical subjects

T P Gordon

Publications and source records attributed to T P Gordon.

At least 19 recordsLinked to original sources

An enhanced chemiluminescence detection system combined with a modified immunoblot technique for the detection of low molecular weight IgM in sera from healthy adults and neonates.

An enhanced chemiluminescence detection system combined with a modified immunoblot technique is described for the detection of low molecular weight IgM (LMW IgM) in human sera and cell culture supernatants at levels down to 2 pg/ml. This detection system is reliable, specific and more sensitive than the previously described chromogenic detection system. Importantly, this method has, for the first time, revealed LMW IgM in the sera from all 34 healthy adults and 26 neonatal cord bloods tested. A significant linear correlation was observed between the LMW IgM and the total circulating IgM in both the healthy adult sera (r = 0.88, p less than 0.001) and cord blood sera (r = 0.98, p less than 0.001).

Adult

Behavioral and physiological response of juvenile sooty mangabeys to reunion with their mothers following a year's absence.

The return of 6 juvenile mangabey monkeys to their social group following an absence of a year resulted in increased basal cortisol secretion for both the offspring and the mothers and in significant decrements in the absolute number of lymphocyte subsets for the offspring. Six 9-month-old sooty mangabeys were removed from their socially housed mothers, subsequently peer housed, and returned to the maternal social group 1 year later. Offspring showed a significant increase in cortisol levels 24 hr following reunion (48 +/- 6%) and this difference persisted through 1 month, while the mothers showed a significant increase only at the 24-hr sample point (18 +/- 3%). Moreover, the offspring, but not the mothers, showed a significant decrease in lymphocyte subsets which were evident through the 1-month sample point. Behavioral data revealed a significant positive correlation between the percent of total scan samples offspring were with their mothers (proximity, contact, huddle) the day of return and the offspring's percent change from baseline in total T cells 24 hr later, r = 0.84. All mother-offspring pairs with the exception of one exhibited frequent affiliative behaviors toward one another by 6 days following the return. These data demonstrate that the reunion of juvenile mangabeys with their mothers after a year's absence is an acute stressor for the mothers and a relatively longer term stressor for the offspring, and that behavioral interactions which characterize the return of individual subjects to the natal group can predict acute physiological responses.

Animals

Social separation and reunion affects immune system in juvenile rhesus monkeys.

Removal of juvenile rhesus monkeys from their natal social group to indoor individual caging resulted in increased basal cortisol secretion and significant decrements in the frequency of lymphoid subpopulations. Fourteen juvenile rhesus monkeys, which had never been removed from the group, were studied. Baseline immune and cortisol measurements were obtained before seven of the subjects were removed from social housing to standard individual cages. The remaining seven subjects, matched for age, sex, weight, and rank, remained in the social group throughout the study serving as controls. Blood samples were taken 24 hours after removal of the test subjects from the group and at specific intervals thereafter through 11 weeks. At 24 hours after the separation test subjects showed a significant increase in basal cortisol levels (40%) and a significant decrease in several immune parameters, with absolute numbers of total T cells declining 72 +/- 12%. Significant group differences in immune parameters persisted through 11 weeks. Eighteen weeks following removal, the test subjects were returned to the group which produced a cortisol rise in both test and controls at the 24-hour postreturn sample. Although there were no group differences in the frequency of lymphoid subsets 24 hours after return, some test subjects showed marked decrements which were inversely related to cortisol and were predicted by behavioral events. These data demonstrate that the removal of naive juvenile rhesus monkeys from their natal social group to individual indoor caging is a potent psychosocial stressor and that the behavioral interactions which characterize the return of the individual subjects to the natal group may predict physiological response.

Animals

Removal from natal social group to peer housing affects cortisol levels and absolute numbers of T cell subsets in juvenile rhesus monkeys.

Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4+ (-56.9%) and CD8+ T cells (-57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation.

Animals

Formation of a new social group of unfamiliar female rhesus monkeys affects the immune and pituitary adrenocortical systems.

Social stress associated with the formation of a new group of rhesus monkeys resulted in increased basal cortisol secretion and significant decreases in immunological parameters. Eight adult female rhesus monkeys, all of which had been raised in social groups, but with no common social history, were simultaneously introduced into an outdoor enclosure along with an adult male. Behavioral data were collected during the introduction and over 9 weeks thereafter. Blood samples were collected prior to and at intervals for 9 weeks following formation. The establishment of a dominance hierarchy, apparent within 48 h, was accomplished with no serious fighting and a complete absence of wounding or trauma. Overall, the group showed a significant increase in cortisol and a significant decrease in the absolute number of total lymphocytes and CD4+ and CD8+ T cells at 24 h postformation, but not thereafter. However, when partitioned into high and low dominance rank, differences in CD4+ and CD8+ T cells were evident for up to 9 weeks with low ranking subjects showing significantly lower values. The housing condition of the subjects immediately prior to introduction, either indoors in individual caging or outdoors in social groups, may have influenced behavior, rank acquisition, and possibly differences in immune parameters. These data demonstrate that social group formation is a potent psychosocial stressor in primates, since stress-sensitive changes were observed in the absence of serious aggression and wounding.

Aggression

Estimation of amounts of anti-La(SS-B) antibody directed against immunodominant epitopes of the La(SS-B) autoantigen.

The contribution of circulating anti-La(SS-B) antibody to the hypergammaglobulinaemia seen in primary Sjögren's syndrome is unknown. In this study levels of anti-La(SS-B) antibody directed against three immunodominant epitopes of the anti-La(SS-B) autoantigen were measured by ELISA in 84 anti-La(SS-B)+ sera using purified recombinant protein and antibody affinity-purified against the three anti-La(SS-B) fusion proteins. There was marked variation in the amounts of IgG anti-La(SS-B) antibody detected, with levels ranging from 0.02 mg/ml to 11 mg/ml. The anti-La(SS-B) levels were greater than 1 mg/ml in 61% of patients; in 18% of sera the anti-La(SS-B) level constituted 10% or more of the total serum IgG. However, other patients were seen with marked hypergammaglobulinaemia and low anti-La(SS-B) concentrations. These results support an antigen-driven mechanism for the anti-La(SS-B) response and suggest that anti-La(SS-B) antibody production is regulated independently of other immunoglobulins.

Antibodies, Antinuclear

Effects of growth hormone on neonatal growth in nursing rhesus monkeys.

The effects of recombinant human GH treatment of either nursing mothers or their infants on neonatal growth in rhesus monkeys was determined. Growth rates of infants treated daily from birth with GH (INFGH; n = 9; 100 micrograms/kg, sc) were compared to those of infants given saline (INFc; n = 10), infants whose mothers received saline from the second trimester of pregnancy through 7 weeks postpartum (CON; n = 9), infants of mothers who received GH during pregnancy only from the second trimester to parturition (PRG; n = 8), infants of mothers who received GH during lactation only from parturition through 7 weeks postpartum (LAC; n = 9), and infants of mothers who received GH during the second trimester of pregnancy through 7 weeks postpartum (PRG/LAC; n = 8). Mothers receiving GH were given 250 micrograms/kg, sc, Monday, Wednesday, and Friday. Infants were allowed to nurse ad libitum. Although infant birth weights were similar among the six groups, body weights at 7 weeks of age were significantly greater in PRG/LAC infants (0.77 +/- 0.03 kg) compared to those in CON (0.66 +/- 0.02 kg), INFc (0.62 +/- 0.03 kg), LAC (0.62 +/- 0.04 kg), and INFGH infants (0.62 +/- 0.01 kg), with infants of PRG mothers intermediate (0.71 +/- 0.02 kg) between them. By 35 weeks of age, after infants had been weaned by their mothers, body weights were similar among all groups. Serum concentrations of insulin-like growth factor-I (IGF-I) rose significantly in all infants during the study period. Although IGF-I levels did not vary significantly among the treatment groups, average concentrations of IGF-I were significantly related to weight gains. Analyses of milk composition revealed that total protein, lactose, and IGF-I levels were similar among groups, whereas the percentage of fat in the milk was significantly higher in PRG/LAC mothers. Milk protein content was significantly related to weight gain. These data suggest that neonatal body weight gain can be accelerated in nursing infants whose mothers have received GH from at least the second trimester of pregnancy through the lactational interval. Since infants of mothers receiving GH during lactation only were not different from controls, the effect of GH in this treatment paradigm may be mammogenic rather than galactopoietic per se.

Animals

Detection of autoantibodies to ribosomal P protein using recombinant autoantigen in a quantitative immunoassay.

Antibodies to ribosomal P proteins are markers for systemic lupus erythematosus (SLE) but are often missed by assays utilizing routine immunofluorescence or immunoprecipitation. Expression of autoantigenic sites encoded by complementary DNA (cDNA) clones offers an inexpensive source of antigen for use in quantitative immunoassays. Using a monospecific ribosomal P positive serum to screen a human placental lambda gt11 expression library, a cDNA clone was isolated which reacted with all anti-P human sera tested. Autoantibodies which were affinity purified from the expressed cDNA reacted with the 38 kDa ribosomal Po protein and reactivity was blocked by absorption with recombinant fusion protein. A stable beta-galactosidase fusion protein of 150 kDa was partially purified by a simple differential centrifugation method and used in an enzyme-linked immunoabsorbent assay to reliably quantitate anti-P responses, with a sensitivity and specificity equal to Western blotting. A survey of 84 normals and 151 patients with autoimmune diseases confirmed the high specificity of anti-P antibodies for SLE. The availability of cloned autoantigen will facilitate more detailed clinico-serologic correlations for anti-P antibodies.

Autoantibodies

Prevalence of natural infection with simian immunodeficiency virus and simian T-cell leukemia virus type I in a breeding colony of sooty mangabey monkeys.

The seroprevalence of antibodies to simian immunodeficiency virus (SIVsmm) and simian T-cell leukemia virus type I (STLV-I) in a captive breeding colony of sooty mangabey monkeys was determined, and infection by SIVsmm was confirmed in all cases by virus isolation. Among 138 animals tested, 57 and 33% were infected with SIVsmm and STLV-I, respectively. While the proportion of female mangabeys (66%) differed significantly (P less than 0.01) from the proportion of male mangabeys (42%) infected with SIVsmm, the proportions of males and females infected with STLV-I were similar, suggesting independent transmission of the two viruses. Among mangabeys less than 1 year old, none were infected with STLV-I and only five of 27 mangabeys, all of which were at least 6 months old when first tested, were infected with SIVsmm. The data document that natural infection of sooty mangabey monkeys with SIVsmm or in association with STLV-I infection does not result in increased disease or mortality, and that transmission of both SIVsmm and STLV-I appears to occur primarily through sexual activity.

Animals

Effects of growth hormone on the tempo of sexual maturation in female rhesus monkeys.

The signal that initiates and maintains the developmental change in LHRH and, consequently, LH secretion in primates, thus regulating the tempo of puberty, is not known. Given the close association between reproductive development and bone maturation, we examined the hypothesis that GH was involved in developmental increases in LH release, specifically by augmenting the decrease in estradiol (E2) negative feedback inhibition of LH that characterizes late puberty in primates. Recombinant human GH (rhGH; 250 micrograms/kg) was given (sc) three times weekly to immature female rhesus monkeys to determine if developmental increases in basal serum LH would occur at an earlier age, and if menarche and first ovulation also would be advanced. The study groups included intact females receiving rhGH (INT + GH; n = 5), intact control animals (INT; n = 6), ovariectomized females receiving E2 plus rhGH (E2OVX + GH; n = 5), and E2-treated ovariectomized control monkeys (E2OVX; n = 4). The females were studied from 20 months of age until their serum LH levels increased (E2OVX groups) or until the occurrence of first ovulation (intact groups). After 12 months of rhGH treatment, the crown-rump lengths were significantly increased, regardless of ovarian status, an effect maintained in the intact females through 21 months of treatment. The mean age at the time of the initial rise in serum LH was advanced by rhGH treatment in intact females (29.6 +/- 0.4 vs. 31.3 +/- 0.3 months), but not E2OVX females. Subsequent maturational elevations in LH secretion were similar in the E2OVS + GH and E2OVX animals even after an incremental increase in E2. Ages at menarche were similar in the INT + GH and INT groups, whereas first ovulation was significantly advanced in three of five INT + GH females (31.5 +/- 0.7 months) compared to that in INT females (43.5 +/- 0.3 months). The remaining INT + GH females ovulated at an age (42.4 +/- 0.4 months) similar to that of INT females. Those females that ovulated by 32 months had higher skeletal maturity scores than the later ovulating INT females, with the other INT + GH females being intermediate. Furthermore, rhGH resulted in a significant increase in serum E2 levels within 12 h of injection, which remained elevated through 24 h. This effect of rhGH on ovarian E2 secretion did not occur until females had shown elevations in basal serum LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors

Season determines timing of first ovulation in rhesus monkeys (Macaca mulatta) housed outdoors.

In order to determine the relative importance of age and season on the occurrence of first ovulation in rhesus monkeys, the timing of puberty in spring-born females (Group S, N = 13) was compared to that of fall (N = 3) and winter-born (N = 5) females (Group W). All females were housed outdoors and were studied from 12 months of age through first ovulation. Menarche occurred at a similar age but significantly earlier in the year for Group W (31.2 +/- 0.7 months; 25 August +/- 19.5 days) than for Group S females (31.2 +/- 0.7 months; 14 November +/- 17.1 days). First ovulation, as assessed from twice weekly serum progesterone determinations, occurred exclusively in the fall or winter in a bimodal age distribution for all females. For Group W females, 6/8 ovulated during the 3rd year at 35.8 +/- 0.7 months while 2/8 ovulated during the 4th year at 45.3 +/- 0.1 months. In contrast, only 3/13 Group S females ovulated during the 3rd year and at a significantly younger age of 31.4 +/- 0.4 months compared to Group W. The remaining Group S females (10/13) ovulated the following autumn at 43.2 +/- 0.2 months, significantly younger than the later ovulating Group W females. In addition to this pattern of first ovulation, serum concentrations of prolactin varied seasonally, rather than with age, in both groups of females with higher levels in the summer and low levels in the winter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry

Short-day melatonin pattern advances puberty in seasonally breeding rhesus monkeys (Macaca mulatta).

Prepubertal, spring-born females (Group H: N = 5) living outdoors were given a daily injection of melatonin (0.70 microgram/kg, s.c.) late in the afternoon to produce a short-day melatonin pattern equivalent to a night of approximately 14 h. The dose of melatonin produced serum concentrations of melatonin which simply extended, within the 24 h day, the normal endogenous nighttime elevation (80-100 pg/ml). The study was started in March when the females were 23 months of age and continued through January. Parameters of sexual maturation for this group were compared to those of untreated, age-matched females (Group C: N = 5) which also lived outdoors under changing environmental conditions. Melatonin treatment significantly advanced age at first perineal swelling (23.9 +/- 0.5 vs 30.5 +/- 0.2 months) and menarche (26.2 +/- 0.9 vs 31.2 +/- 2.4 months). Since all of the females were spring-born, these events occurred earlier in the year in Group H females (swelling: April vs October; menarche: June vs November). Furthermore, 4/5 Group H females exhibited first ovulation in December at 31.8 +/- 0.3 months. None of the Group C females ovulated during their 2nd year, but all did so the next breeding season at 43.5 +/- 0.3 months. All first ovulations in females had luteal-phase progesterone concentrations elevated for at least 12 days with peaks greater than 3.0 ng/ml. Body weights were similar between groups until the post-menarchial interval when weight gain was greater in the melatonin-treated females. A similar pattern of group differences also was observed for serum concentrations of growth hormone and somatomedin-C. In addition, prolactin concentrations were seasonally elevated during the summer months in both groups, but concentrations fell to nadir values by August in Group H females and remained elevated until October in Group C animals. These results suggest that, in adolescent females housed outdoors, exposure to a short-day melatonin pattern permits sexual maturation to be initiated at an earlier age, allowing first ovulation to occur in the months immediately after menarche. A long-day melatonin pattern, typically experienced by females at this developmental age, may actually delay the initiation of maturational events until the subsequent fall months.

Animals

Nocturnal changes in serum melatonin during female puberty in rhesus monkeys: a longitudinal study.

Diurnal concentrations of serum melatonin were determined longitudinally in female rhesus monkeys throughout sexual maturation to ascertain how levels varied with advancing age and reproductive onset. Females were housed either in outdoor enclosures (n = 8) exposed to ambient environmental conditions, or indoors (n = 4) under a photoperiod of 12 h light: 12 h darkness and fixed temperature of 20-23 degrees C. Animals were studied from immaturity (15 months) through first ovulation and were additionally compared with fully adult female rhesus monkeys (n = 5) studied during the annual breeding season. The diurnal melatonin pattern was described for the developing females in the summer, autumn and winter in 3 successive years from samples collected at 10.00, 18.00, 22.00, 02.00, 06.00 and 10.00 h. Nocturnal levels of melatonin declined significantly during development in both indoor- and outdoor-housed females with a progressive decrease up to 33 months of age. Daytime values were consistently low but exhibited a slight decline also with age. Nocturnal values in all months sampled fell significantly with greater decreases occurring at the earliest ages. Furthermore, superimposed upon this developmental change, animals housed outdoors responded to seasonal changes in photoperiod with diurnal increases in melatonin occurring after sunset. The females in the present study exhibited first ovulation at two distinct ages: 32-37 months ('early', n = 6) and 41-45 months ('later', n = 5). One female did not ovulate within the study period. Although nocturnal levels of serum melatonin were similar between the two groups up to 29 months of age, a post-hoc analysis revealed that concentrations were significantly lower by 34 months of age for the early group, a time coincident with first ovulation. Nocturnal levels of melatonin remained high, relative to the early group, in the later ovulating females until 43 months of age, coincident with first ovulation for these animals. The diurnal pattern of serum melatonin at first ovulation, regardless of chronological age, was similar to that observed during the ovulatory season for adult female rhesus monkeys. These data suggest that nocturnal melatonin concentrations decline with advancing chronological age in prepubertal female rhesus monkeys.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Primates.

Nonhuman primates demonstrate marked similarities to humans in almost all aspects of their anatomy, endocrinology, and physiology. These similarities underlie the value of these animals for appropriate studies in neurobiology, immunology, pathology, reproductive biology, teratology, neonatology, endocrinology, cardiology, and psychology. Investigations with nonhuman primates has made, and continues to make, significant contributions to biomedical and behavioral research. This review provides an overview of basic and applied studies for which primates are appropriate subjects and a summary of the advantages and problems of using nonhuman primates in research.

Aging

Prolonged lactational infertility in adolescent rhesus monkeys.

The present study examined the effects of first pregnancy and nursing behavior on postpartum infertility in seasonally breeding rhesus monkeys to assess whether prolonged lactational infertility observed in adolescent mothers is due to a particular pattern of nursing or to decrements in body growth rates. After a successful first pregnancy, a significant percentage of the lactating adolescent mothers (57.1%; n = 8) failed to exhibit an ovulation with normal luteal phase during the subsequent breeding season. In contrast, the remaining lactating adolescents (42.9%, n = 6) and all of the adult mothers (100%, n = 6) exhibited ovulations with a normal luteal phase. Age alone was not the critical variable, since all nonlactating adolescents exhibited ovulations with normal luteal phase parameters in the subsequent breeding season. The luteal phase abnormalities exhibited by the subset of lactating adolescent females were characterized by an inadequate luteal phase (ILP) and by significantly lower serum levels of progesterone, estradiol, and bioactive luteinizing hormone. The occurrence of these ILP ovulations was associated with more frequent nursing bouts prior to ovulation and during the subsequent luteal phase. In contrast, nursing patterns for adult females who had ovulations with normal luteal phases were more similar to those of the infertile lactating adolescents exhibiting significantly longer and more frequent nursing bouts, suggesting that fully adult females may be less sensitive to the inhibitory aspects of a suckling stimulus. Differences in luteal phase function among lactating adolescents were not related to differential rates of ponderal or skeletal growth. A still-developing neuroendocrine system may thus render a significant proportion of adolescent females more sensitive to suckling-induced suppression of gonadotropin secretion.

Animals

Effects of a natural versus artificial environment on the tempo of maturation in female rhesus monkeys.

To identify factors that regulate the tempo of growth and puberty, the present study examined how the environment influenced the timing of menarche and first ovulation in rhesus monkeys and how these events were related to differential rates of growth. Spring-born females were raised from 12 months of age under natural outdoor conditions (OH; n = 6) or indoors (IH; n = 9) under a controlled photoperiod (12h of light, 12h of darkness) and temperature (20-23 C). Ages at the initial increases in serum bioactive LH levels (27.7 +/- 0.7 vs. 31.4 +/- 1.0 months), menarche (26.0 +/- 0.7 vs. 32.5 +/- 0.9 months), and first ovulation (33.9 +/- 1.4 vs. 43.5 +/- 0.3 months) were significantly advanced in IH compared to OH females. First ovulation for the OH females occurred exclusively in October and November of the fourth year, whereas the distribution of first ovulation of IH females was biomodal, with seven of nine occurring in November or December at 31.8 +/- 0.5 months, and two of nine ovulating in September or October at 41.2 +/- 0.5 months. Serum levels of PRL varied seasonally in OH females throughout development, with peaks in July and nadirs in October. A similar rhythm was observed for IH females during the first 12 months of indoor housing, after which point the period decreased from 11.9 +/- 0.5 to 9.3 +/- 0.6 months. Overall increments in body weight did not differ between groups. An acceleration of growth in both crown-rump and tibial lengths occurred just before menarche in both groups, and this occurred at about 26 months for IH and about 32 months for OH females. Skeletal maturity was significantly advanced at 27 months in IH females and at every chronological age thereafter. Serum concentrations of somatomedin-C and GH paralleled group differences in bone maturation. Both hormones were significantly elevated by 16-18 months of age in IH animals compared to OH females and remained so until 34-36 months of age. Although a distinct seasonal rhythm in both GH and somatomedin-C was evident in OH animals, no such pattern was observed in IH females. These data suggest that exposure to an outdoor environment moderates the tempo of both sexual and skeletal maturation. The acceleration in reproductive development in animals exposed to a constant environment was associated with an acceleration in bone maturation, suggesting that common factors may be responsible for the initiation of both events.

Aging

The effect of season on the induction of sexual behavior by estradiol in female rhesus monkeys.

Rhesus monkeys housed in an outdoor environment are seasonal breeders, with ovulations and concomitant sexual behavior limited to the fall and winter months. To determine if there is a seasonal difference in the capacity of physiological levels of estradiol (E2) to induce sexual behavior in ovariectomized rhesus monkeys housed outdoors, subjects living in a social group were treated with subcutaneous E2 implants in a counter-balanced design during the nonbreeding season (May-July) and during the breeding season (September-November). Serum E2 levels were monitored by obtaining blood samples twice a week. Three levels of E2 were studied: baseline (less than 30 pg/ml), follicular (100 pg/ml), and periovulatory (200 pg/ml). Two of five adult males in the group were injected with human chorionic gonadotropin (hCG) twice a week to insure that males with high testosterone levels were present during each season. Focal observations of behavior of 15 minutes' duration on each subject were conducted 5 days per week, with frequencies and durations of social, sexual, and solitary behaviors recorded. Concomitant 2-h group scans were made to record all occurrences of mounting behavior. Neither heterosexual serial mounting nor seminal plugs were ever observed in E2-treated females during the summer months. In contrast, copulation and seminal plugs were observed in subjects at both treatment levels during the fall. While E2-treated females engaged in homosexual mounting behavior during both summer and fall, E2 treatment resulted in heterosexual copulation only during the fall. Changes in patterns of social behavior paralleled changes in sexual behavior and were significantly affected by treatment and season, with more male-female interactions during the fall months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Seasonal modulation of luteinizing-hormone secretion in female rhesus monkeys.

The seasonal restriction of ovulations in rhesus monkeys is thought to be due to enhanced estradiol (E2)-negative feedback suppression of luteinizing hormone (LH) during the spring and summer anovulatory months. This hypothesis was examined in seven ovariectomized monkeys housed in an outdoor environment and treated with various doses of E2 in a counterbalanced design during both the anovulatory season (May-Jul) and the breeding season (Sep-Nov). Subcutaneous implants of E2 produced levels that mimicked late follicular (LF-100 pg/ml) or periovulatory concentrations (PO-190 pg/ml). Analyses of twice weekly serum samples revealed that during the period of no E2 treatment (NT), basal levels of bioactive LH were significantly lower in the summer than the fall. Although treatment with both doses of E2 lowered basal LH levels during both seasons, the decrease in LH was significantly greater during the summer. Samples collected at 15-min intervals for 2 h revealed that during NT, LH pulses were significantly slower during the summer than in the fall, whereas pulse amplitude did not differ between seasons. Treatment with both doses of E2 either abolished or significantly reduced both LH pulse amplitude and frequency in the summer. In contrast, LH pulses during the fall were not affected by E2 treatment. Response to treatment with LH-releasing hormone (5 micrograms/kg i.v.) revealed that release was significantly reduced during E2 treatment in the summer. These data indicate that seasonal changes in the environment influence both nongonadal control and E2-negative feedback inhibition of LH secretion. The reduced ability of E2 to maximally suppress LH release in the fall can thus account for the seasonally delimited pattern of ovulations observed in rhesus monkeys.

Animals