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Biomedical subjects

M K McClintock

Publications and source records attributed to M K McClintock.

At least 19 recordsLinked to original sources
PubMed2005

Frequent serial fecal corticoid measures from rats reflect circadian and ovarian corticosterone rhythms.

The circadian glucocorticoid rhythm provides important information on the functioning of the hypothalamic-pituitary-adrenal axis in individuals. Frequent repeated blood sampling can limit the kinds of studies conducted on this rhythm, particularly in small laboratory rodents that have limited blood volumes and are easily stressed by handling. We developed an extraction and assay protocol to measure fecal corticosterone metabolites in repeated samples collected from undisturbed male and female adult Sprague-Dawley rats. This fecal measure provides a non-invasive method to assess changes in corticosterone within a single animal over time, with sufficient temporal acuity to quantify several characteristics of the circadian rhythm: e.g. the nadir, acrophase, and asymmetry (saw-tooth) of the rhythm. Males excreted more immunoreactive fecal corticoids than did females. Across the estrous cycle, females produced more fecal corticoids on proestrus (the day of the preovulatory luteinizing hormone surge) than during estrus or metestrus. These results establish a baseline from which to study environmental, psychological, and physiological disturbances of the circadian corticosterone rhythm within individual rats.

Adrenal Cortex Hormones↗
PubMed2003

Fear of novelty in infant rats predicts adult corticosterone dynamics and an early death.

Individuals who are fearful of novelty have a larger hypothalamic-pituitary-adrenal axis response than do nonfearful individuals. We hypothesized that a fearful behavioral style emerging early in life would be associated with life-long altered adrenal activity. Because there is ample physiological evidence both costs and benefits of adrenal activation, we determined whether such a stable emotional-neuroendocrine trait was associated with differential morbidity and mortality. To conduct such lifespan work, we studied a relatively short-lived mammal: the Norway rat. We first established that an animal's hesitation or willingness to explore a novel environment ("neophobia" and "neophilia," respectively) is an identifiable and stable behavioral trait in young-adult males and that neophobia, compared with neophilia, was associated with a greater glucocorticoid response to novelty. Second, we were able to detect behavioral differences among infant rats within a family, and this behavioral disposition at infancy predicted the magnitude of the glucocorticoid response in late middle age. Males identified as neophobic during infancy died sooner than their less fearful brothers. Although both types of males died with similar pathologies (tumors), neophobic males were 60% more likely to die at any point in time. This lifespan study identifies an emotional trait in infancy that predicts an early death and an associated neuroendocrine trait in adulthood that is a potential mechanism underlying the relationship between behavioral style and longevity.

Adrenal Glands↗
PubMed2001

Sustained human chemosignal unconsciously alters brain function.

The human chemosignal, Delta 4,16-androstadien-3-one modulates psychological state without being consciously discernible as an odor. This study demonstrates that Delta 4,16-androstadien-3-one (androstadienone) alters cerebral glucose utilization both in subcortical regions and in areas of the neocortex not exclusively associated with olfaction. These widely distributed changes are consistent with modulation of an integrated neural network for regulation of emotional and attentional states. This is the first study to demonstrate the effects of a sustained chemosignal on brain metabolism and to show that they are similar to those of long acting chemical substances that affect psychological states. Moreover, this provides the first evidence that a human chemosignal has distributed effects on cortical processes and brain metabolism even when it is not detected consciously.

Adult↗
PubMed2001

Variation in reproductive traits is associated with short anogenital distance in female rats.

Anogenital distance was used as a biomarker for natural variation in prenatal androgenization of female rats and was associated with individual differences in a suite of reproductive characteristics. Females with short anogenital distances were likely to have first vaginal estrus earlier than females with longer anogenital distances and to have first vaginal estrus on the same day as vaginal opening. In young adulthood, females with short anogenital distances had shorter ovarian cycles and less intense lordosis reflexes in response to manual palpation than those with longer anogenital distances, but only when living individually, not in groups. Taken together, these findings indicate that prenatal androgenization affects reproductive traits throughout the life span.

Anal Canal↗
PubMed2000

Location and gross morphology of the nasopalatine duct in human adults.

OBJECTIVE: To characterize the nasal opening of the human nasopalatine duct (NPD; a major duct of the vomeronasal system used in animals for chemical communication) by identifying its location, categorizing variations in physical characteristics, and assessing frequency of detection. DESIGN: Two studies: (1) general study incorporating endoscopic examinations documented by videotapes and photographs, and an investigation of detection bias in terms of method of visualization and defining criteria for NPD identification; and (2) cadaver dissections examining NPD gross anatomy and proximity to the putative vomeronasal organ (VNO), the second major duct of the vomeronasal system. SETTING: Department of Otolaryngology, University of Chicago Hospitals, Chicago, Ill. SUBJECTS: A total of 125 university community volunteers, with a mean age of 23 years. RESULTS: (1) General study: NPD was located 1.9+/-0.02 cm (mean+/-SEM) dorsal to the columella nasi, and 0.2+/-0.01 cm above the nasal floor/septum junction, in both nostrils (90% bilateral), and was symmetrical in shape. An NPD was detected in 94% of 221 nostrils unobstructed in the region of interest. Fossa shapes were oval (57%), round (18%), spindle-shaped (18%), and tubular (7%). A small, round aperture was visualized in 30% of fossae. Among 3 observers, NPD detection frequency ranged from 94% to 40%, with the disparity due to inclusion of different defining characteristics. (2) Cadaver dissection study: bilateral nasal NPD fossae were found in every specimen probed to maximum approximate depth of 8 mm. No buccal pits associated with patent NPD were detected. Putative VNOs superior and just anterior to NPD fossae were detected in fewer than half the specimens. CONCLUSIONS: The nasal opening of the NPD is bilateral and symmetrical, located at the base of the nasal septum. Unusually contradictory anatomical descriptions in the human putative VNO literature may be attributable to inexact descriptions or misidentification of structures. The function of NPD remains controversial.

Adolescent↗
PubMed2000

Psychological state and mood effects of steroidal chemosignals in women and men.

We tested the hypothesis that isolated steroids, claimed to act like pheromones, affect human psychological state or mood. In the first experiment, we established that two steroids, Delta4, 16-androstadien-3-one and 1,3,5(10)16-estratetraen-3-ol, modulated emotional states within 6 min of exposure. In men and women, neither steroid had specific effects on states of alertness or negative-confused mood. However, both steroids increased positive stimulated mood state in women but decreased it in men. These psychological findings do not parallel the reported sexually specific effects of these two steroids on the surface potential activity of putative vomeronasal epithelium. In a second experiment on women, we replicated that Delta4,16-androstadien-3-one modulated their general mood state, even when women were not aware of its odor and gave identical olfactory descriptions for the steroid and the control carrier solutions. In this within-subjects, repeated-measures experiment, androstadienone prevented the deterioration in general mood which occurred during exposure to the clove oil carrier solution in the laboratory environment. Thus, androstadienone appears to modulate affect, rather than releasing stereotyped behaviors or emotions. It is premature to call these steroids human pheromones. They are nonetheless psychologically potent, mandating future work delineating their function-i.e., whether these steroids are communicative chemosignals, context specific, or related to unconscious associations. In light of these modulatory effects and the complexity of human behavior, the function of chemosignals and pheromonal systems in a variety of species may need to be expanded to include the concept of modulators, as well as the traditional releasers, primers, and signaling compounds.

Adult↗
PubMed2000

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Humans↗
PubMed2000

Multilevel integrative analyses of human behavior: social neuroscience and the complementing nature of social and biological approaches.

Social and biological explanations traditionally have been cast as incompatible, but advances in recent years have revealed a new view synthesized from these 2 very different levels of analysis. The authors review evidence underscoring the complementing nature of social and biological levels of analysis and how the 2 together can foster understanding of the mechanisms underlying complex behavior and the mind. Specifically, they review the utility of considering social influences on biological processes that are often viewed as outside the social domain including genetic constitution, gene expression, disease, and autonomic, neuroendocrine, and immune activity. This research underscores the unity of psychology and the importance of retaining multilevel integrative research that spans molar and molecular levels of analysis. Especially needed in the coming years is more research on the mechanisms linking social and biological events and processes.

Forecasting↗
PubMed1999

Sex ratio bias in postpartum-conceived Norway rat litters is produced by embryonic loss in midpregnancy.

In rats, dams that conceive in their postpartum oestrus and then lose their firstborn litter bias the sex ratio of the litter toward females in utero. The present study identifies the source of litter sex ratio bias in these postpartum pregnant non-lactating dams. The female bias arises first through the postconception loss of embryos, and second, the loss occurs in midpregnancy between the attachment of the blastocyst to the uterine wall on day 5 and full metrial gland development on day 14. Some pregnancies were restricted to one uterine horn to see if this loss (and thus the opportunity for litter sex ratio biasing) was influenced by local factors operating within the uterine horn. Embryonic loss was more closely associated with the number of embryos implanting in a single horn than with the number implanting in the litter, demonstrating that local crowding within a horn is sufficient for the preferential loss of male embryos. This loss did not cause an obvious decrease in the size of the live-born litter because only those horns with a surfeit of embryos lost them. This process was the same in the right and left horns; both carried and lost the same numbers of embryos. A dam that conceives in her postpartum oestrus and then loses her suckling litter forgoes the implantation delay and uterine healing caused by lactation. Male embryos are less successful at implanting in a uterus only recently vacated by a previous litter.

Animals↗
PubMed1998

On the nature of mammalian and human pheromones.

Communication by chemical (pheromone) signals is important in many species, including mammals. Chemosensory and hormonal systems can interact in at least two ways: (i) chemosensory input, especially but not exclusively that through the vomeronasal organ, may elicit hormonal release, which, in turn, may facilitate behavioral or physiological responses; and (ii) hormones, especially steroids, may be essential for some responses to chemosensory, including vomeronasal, input. Recent, still controversial reports, suggest that chemosensory communication may occur in humans via a residual vomeronasal organ and that chemosensory/hormonal interactions also operate in humans. In this symposium these matters are examined critically. Johnston explores the concept of pheromone communication and suggests that the notion of a single-chemical 'magic bullet' irresistibly leading to a preprogrammed result is too simplistic despite documented examples of special stimuli acting via the vomeronasal organ. Meredith briefly reviews evidence for hormonal mediation of the effects of vomeronasal input; including a situation where vomeronasal and hormonal facilitation of a behavior appear to be interchangeable--but where vomeronasal input appears important only in inexperienced animals. Wood discusses evidence that the effectiveness of chemosensory input to particular brain nuclei depends critically on the simultaneous presence of a steroid hormone within the same nucleus. Monti-Bloch presents his evidence that steroids may act as gender-specific chemical signals in humans, exciting an electrical response from the residual human vomeronasal organ and affecting human hormone levels.

Animal Communication↗
PubMed1998

Regulation of ovulation by human pheromones.

Pheromones are airborne chemical signals that are released by an individual into the environment and which affect the physiology or behaviour of other members of the same species. The idea that humans produce pheromones has excited the imagination of scientists and the public, leading to widespread claims for their existence, which, however, has remained unproven. Here we investigate whether humans produce compounds that regulate a specific neuroendocrine mechanism in other people without being consciously detected as odours (thereby fulfilling the classic definition of a pheromone). We found that odourless compounds from the armpits of women in the late follicular phase of their menstrual cycles accelerated the preovulatory surge of luteinizing hormone of recipient women and shortened their menstrual cycles. Axillary (underarm) compounds from the same donors which were collected later in the menstrual cycle (at ovulation) had the opposite effect: they delayed the luteinizing-hormone surge of the recipients and lengthened their menstrual cycles. By showing in a fully controlled experiment that the timing of ovulation can be manipulated, this study provides definitive evidence of human pheromones.

Adult↗
PubMed1998

Whither menstrual synchrony?

The initial report of menstrual synchrony indicated that social interactions among groups of women could regulate their ovarian cycles. The initial focus on menstrual synchrony was just the beginning of a discovery process, not all facets of the whole phenomenon. Menstrual synchrony was similar to an archeologist finding a fossilized tooth, which demonstrated the existence of a prehistoric creature. Menstrual synchrony could have turned out to be like the chronodonts, prehistoric creatures for which we still have only their fossilized teeth as evidence for their existence. Fortunately, after almost 3 decades of work, we have excavated the site and been able to unearth more about the structure of this particular creature. It is social regulation of ovulation throughout the lifespan--a creature made up not only of menstrual synchrony, but various forms of the timing of spontaneous ovulatory cycles in adults. It also includes the social regulation of ovulation at other points during the reproductive lifespan: puberty, inter-birth intervals and reproductive senescence. Menstrual synchrony is but one indicator of the phenomenon; it is now clear that there is a great deal more to it than was seen at the time of the original report.

Adolescent↗
PubMed1997

Ovulatory pheromone shortens ovarian cycles of female rats living in olfactory isolation.

McClintock found that female rats living in isolation or in groups synchronized their ovarian cycles, and she proposed a two-pheromone mechanism to explain synchrony: one pheromone shortens cycles and the other lengthens them. Subsequent research revealed that the preovulatory pheromone shortened cycles, whereas the ovulatory pheromone lengthened cycles. Schank and McClintock modeled this mechanism with computer simulation, assuming variability in sensitivity to pheromones during the ovarian cycle, and found that a coupled-oscillator mechanism can synchronize cycles, if pheromone sensitivity is highest around the time of ovulation. In this paper, we report the effects of pulses of ovulatory pheromone on the ovarian cycles of isolated female rats. Donor females were in the ovulatory phase of their cycle and recipient females were in olfactory isolation except during specified phases of their ovarian cycles. Recipient females showed significant shortening in ovarian cycles, with no significant variability in sensitivity to the ovulatory pheromone during the ovarian cycle. We discuss these conflicting results in terms of the experimental context of recipient females and the components and complexities of pheromone signals.

Animals↗
PubMed1995

Endocrine basis for two types of individual differences in lordosis reflex intensity.

We have identified individual differences in two independent types of lordosis reflex intensity. Overall lordosis reflex intensity, averaged across 9.4 +/- 0.99 days (range = 1-18 days), differs among cycling individuals and is a biomarker for the rate and pattern of reproductive aging. Although estrogen is necessary to permit lordosis reflex responding and manifests individual differences throughout the estrous cycle, it was individual differences in progesterone that correlated negatively with the individual variation in overall lordosis reflex intensity; females with intense overall lordosis reflexes had low progesterone throughout the estrous cycle. Independent of their overall reflex intensity, females also displayed individual variation in lordosis reflex intensity on proestrus. Among females that still maintained a cyclic lordosis reflex, those with intense lordosis reflexes on proestrus had high levels of luteinizing hormone (LH) at lights out. Among females that displayed intense lordosis reflexes throughout the estrous cycle (i.e., had entered constant lordosis), those with intense proestrous lordosis reflexes had low levels of LH at lights out on proestrus. Females who had entered constant lordosis tended to have lower overall progesterone than females who still maintained cyclic patterns of lordosis. Thus, constant lordosis was identified as an important component of the changes of reproductive aging.

Animals↗
PubMed1994

Multiple factors determine the sex ratio of postpartum-conceived Norway rat litters.

When Norway rat litters are nursed communally, postpartum-conceived litters born asynchronously are female biased at birth. To determine if one or more mechanisms produced this sex ratio bias, we studied litters conceived at a postpartum estrus, and systematically varied the presence or absence of a litter suckling during gestation. Four different factors biased the sex ratio of postpartum-conceived litters. Postpartum condition, implantation in a single uterine horn, and very large litter size favored the birth of female pups. The presence of suckling pups during gestation, on the other hand, brought the sex ratio up to parity. Each factor operated at or before implantation, and apparently did so asymmetrically in the two horns of the uterus. Thus, a litter's sex ratio at birth, even a sex ratio of parity, can be the result of multiple mechanisms of bias, some working in opposition to each other. Theories of sex ratio biasing must incorporate multiple mechanisms rather than focusing on single mechanisms within a given species.

Animals↗
PubMed1993

Individual differences among female rats in the timing of the preovulatory LH surge are predicted by lordosis reflex intensity.

In young female rats, we found individual differences in LH surge characteristics that could underlie differences in fertility throughout adulthood and aging. We modified a jugular cannulation technique, which enabled us to characterize four successive proestrous LH surges in regularly cycling female rats. During a surge, the timing and amount of LH were negatively correlated, so that late-onset surges reached a low peak, late in the day. Within a female rat, the timing of the LH surge, but not the blood level of LH, was stable from cycle to cycle. Thus, differences in onset and peak time between successive LH surges within one female were less than differences among females. Moreover, these individual differences in timing of the LH surge were positively correlated with individual differences in lordosis reflex intensity on proestrus. Females with early-onset LH surges had high average lordosis reflex intensity on proestrus. Therefore, lordosis reflex intensity is a nonintrusive behavioral biomarker for individual differences in the timing of the preovulatory LH surge. This relationship between behavior and the preovulatory LH surge may reflect a hormonal basis for variations in reproductive strategies throughout the life span.

Animals↗