Circamensal Rhythms in Physical Performance

The eumenorrheic menstrual cycle represents a clear inherent biological rhythm that might interact with both physical performance, and/or the physiological response to performance. The predominant hormonal fluctuations throughout the cycle are in the ovarian steroids oestrogen and progesterone. Progesterone has both a thermogenic and ventilatory effect leading to a potential increase in minute ventilation and body temperature during exercise. Oestrogen has been linked to fluctuations in blood flow and heart rate via a vasodilatory mechanism, plus potential variation in muscle strength. If these hormones do indeed influence physical performance, or the physiological response to performance, female athletes might choose to manipulate the cycle through an endogenous hormonal mechanism. Furthermore, researchers utilizing a female population must control for these fluctuations in their research design.     

Does the response to cocaine differ as a function of sex or hormonal status in human and non-human primates?

Stimulant abuse continues to be a growing problem among women. Over the last 10-15 years, an increasing number of studies have focused on factors that may be implicated in stimulant abuse in women as compared to men, including the role of hormonal fluctuations across the menstrual cycle. Numerous preclinical studies have documented that female rodents are more sensitive than male rodents to the behavioral effects of stimulant administration and the hormone estradiol is involved in the enhanced response to stimulants observed in females. In contrast, fewer studies have been conducted in humans and non-human primates addressing the role of sex and gonadal hormones on the effects of cocaine. This review paper presents a recent update on data collected in our Human Cocaine Challenge Laboratory and our Non-human Primate Laboratory, including analysis of cocaine pharmacokinetics, sex differences, the menstrual cycle, and the role of progesterone in modulating the response to cocaine. Our studies indicate that there is minimal evidence that the response to intranasal cocaine varies across the menstrual cycle or between men and women. In contrast, the response to smoked cocaine is greater in the follicular phase than the luteal phase and differences between men and women generally only emerge when men are compared to women in the luteal phase. In terms of potential hormonal mechanisms for these differences, the hormone progesterone attenuates the subjective response to cocaine. With respect to cocaine self-administration, there are minimal changes across the menstrual cycle in both humans and non-human primates. Thus, there is converging evidence across a range of species that the behavioral effects of cocaine (1) differ between males and females, (2) differ in relation to hormonal fluctuations, (3) can be attenuated by progesterone (at least in females), and (4) do not appear to be related to differences in cocaine pharmacokinetics.     

Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution (1)H NMR spectroscopy of urine and pattern recognition

Metabonomic methods utilizing (1)H NMR spectroscopy and pattern recognition analysis (NMR-PR) have been applied to investigate biochemical variation in a control population of female rats over time in relation to diurnal and estrus cycle fluctuations. Urine samples were collected twice daily (6 AM-6 PM and 6 PM-6 AM) from female rats (n = 10) for a period of 10 days. (1)H NMR spectroscopic analysis and PR were performed on each sample. Subtle differences in the endogenous metabolite excretion profiles of urine samples at the various stages of the estrus cycle were observed. The main inherent metabolic clustering in the principal components analysis (PCA) maps was related to interrat variation and was observed in the first two principal components (PCs), accounting for 66% of the variance in these data. Separation of urinary data according to time of sampling (day and night) was achieved in the lower PCs. Some of the differences in the urinary profiles of day and night samples causing this separation were attributed to the increase in metabolic activity of the rat during the night. Individual rat data were also mapped as a function of time, using PCA, to produce a metabolic trajectory, which in a number of cases facilitated separation of one or more stages of the estrus cycle. Several of the fluctuations observed between urine samples collected during the different stages of the estrus cycle may be related to hormone levels. Although variation in metabolite profiles relating to both diurnal and hormonal variation could be detected these perturbations were minor compared with the effects observed due to interrat variation. This is the first time that a hormonal cycle has been described for individuals based on NMR spectroscopic and multivariate analysis of metabolic data and shows the value of metabonomic methods in the investigation of physiological variation and rhythms.     

Is there energy conservation in amenorrheic compared with eumenorrheic distance runners?

The female distance runner is considered at high risk for secondary amenorrhea and reduced spinal bone mineral, and recent studies have suggested that these disturbances might be nutritionally or metabolically linked. The present study investigated 1) whether there is a physiological basis by which the amenorrheic runner might maintain weight at a lower than expected caloric intake, i.e., conservation of energy, and 2) the potential interactions of reduced energy intake, secondary amenorrhea, and reductions in bone density. Subjects included 13 elite female distance runners, 8 amenorrheic and 5 eumenorrheic, and 5 untrained female controls. Body composition by hydrostatic weighing, bone density and mineral content by dual-photon absorptiometry, and blood samples for hormonal analyses (once per week for 4 wk) were obtained, as were duplicate measures for resting metabolic rate, thermic effect of a meal, and the energy cost of specific (treadmill) and nonspecific (cycle ergometer) physical activity. Energy intake and energy expenditure were estimated by 3-day logs. Energy intakes did not differ (1,781, 1,690, and 1,763 kcal), nor did energy expenditures (2,480, 2,314, and 2,268 kcal), for the amenorrheic and eumenorrheic runner and control groups, respectively. The difference between reported energy intake and estimated energy expenditure of 500-700 kcal was likely due to underreporting or restricting intake, inasmuch as there was no evidence of energy conservation. A possible link was suggested between disordered eating, secondary amenorrhea, and bone mineral loss.     

Effects of progesterone and estradiol on the proliferation of phytohemagglutinin-stimulated human lymphocytes

In this paper we report on a study to elucidate whether the response of human lymphocytes to mitogenic stimulation was modified by physiological changes which occur during the menstrual cycle. Experiments with untreated cultures showed intra-individual variation to mitogen stimulation in female lymphocyte cultures, but a significant correlation between the menstrual cycle and the proliferation kinetics of lymphocytes was not found. Consequently, we performed experiments in which two of the hormones that regulate the menstrual cycle in women, estradiol and progesterone, were added to cultured human lymphocytes obtained from both men and women. The results indicate that both hormones at physiological concentrations have the capacity to modify the proliferation of PHA-stimulated human lymphocytes. Therefore, both hormones could play a role in the induction of the intra-individual variation observed in the untreated female cultures. However, in vivo other factors could also modify the proliferation kinetics of human lymphocytes preventing the demonstration of the effects of a single factor, such as the hormonal changes occurring during the menstrual cycle.     

The Effects of Sex Hormonal Fluctuations during Menstrual Cycle on Cortical Excitability and Manual Dexterity (a Pilot Study)

Aim

To investigate whether hormonal fluctuations during the menstrual cycle affect corticospinal excitability, intracortical inhibition (ICI) or facilitation (ICF) in primary motor cortex, and also whether the hormonal fluctuations have any effect on manual dexterity in neurologically intact women.

Materials and Methods

Twenty volunteers (10 Female, 10 Male) were included in this study. The levels of progesterone and estradiol were measured from saliva during the women’s menstrual follicular, ovulation and mid-luteal phases. Motor evoked potentials were recorded from the right first dorsal interosseous muscle. Single and paired-pulse Transcranial Magnetic Stimulation (TMS) were delivered in a block of 20 stimuli. With paired-pulse technique, 3ms and 10ms inter-stimulus intervals were used to assess ICI and ICF, respectively. The Grooved Pegboard Test (GPT) was completed in each session before the TMS assessments. Male participants were tested at similar time intervals as female participants.

Results

Mixed design ANOVA revealed that GPT score in female participants was significantly lower at the mid-luteal phase compared to the ovulation phase (p = 0.017). However, it was not correlated with progesterone or estrogen fluctuations during the menstrual cycle. The results also showed that the effect of phase, sex and the interaction of phase by sex for resting motor threshold, ICI or ICF were not significant (p > 0.05).

Conclusion

Manual dexterity performance fluctuates during the menstrual cycle in neurologically intact women, which might be due to the balance of the neuromodulatory effects of P4 and E2 in the motor cortex during different phases.     

Loss of estrus in human evolution: Too many answers,too few questions

Models addressing the importance of “loss of estrus” in human evolution assume that, as part of a general trend among higher primates, endogenous hormonal fluctuations have less influence on human female sexuality than cognitive and socioenvironmental factors. The diversity of reproductive patterns among primate species is not satisfactorily explained as the outcome of evolutionary trends along dimensions such as brain enlargement, behavioral flexibility, or relative independence of behavior from physiology. Rather, the role of hormones and other factors must be viewed in the context of species' life history and ecological constraints. Human studies on the relationship between the menstrual cycle and sexual behavior have been limited to Western women in industrialized societies, which may not reveal evolved behavioral-physiological patterns. Furthermore, available studies have yielded inconsistent results. No single pattern emerges that can be said to characterize the human female, and no conclusion can be reached regarding the relationship between cyclic hormonal fluctuations and sexual behavior and, thus, whether human ovulation is concealed. Future studies are needed that are methodologically improved and systematically document the interaction among ecological, subsistence, social, and physiological variables.     

Evidence for "memory" of cervical stimulation for the promotion of pregnancy in rats

Successful pregnancy in the female rat depends upon two sets of physiological events: (1) transport of gametes (sperm and egg) through the reproductive tract so that fertilization can be effected and (2) establishment of an appropriate hormonal environment (progestational state) so that the fertilized egg can implant in the uterus and be maintained during subsequent gestation. This study highlights the independence of the mechanisms controlling the gametic and hormonal aspects of pregnancy by temporally separating the introduction of sperm into the female from the stimulation that triggers the progestational hormonal response. The progestational state was initiated by electrical stimulation of the cervix, and sperm was introduced directly into the uterus by artificial insemination. Although these two events were separated by up to 3 days, pregnancy could ensue. Cervical stimulation, normally a consequence of male intromission behavior, establishes a condition in the central nervous system, a "memory" that signals the probable induction of pregnancy. Without this "memory," animals with a short estrous cycle would continue to cycle after mating, thereby producing a hormonal environment incompatible with implantation. The "memory" is manifested by daily surges of prolactin irrespective of fertilization. This is the first physiological demonstration that a "memory" of cervical stimulation can be called upon to support a viable pregnancy.     

Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women

Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC-related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre-menopausal women using the CHC pill, compared to the control group of nine age-matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive-related changes of the gut microbiota and the potential implications of these changes for women's health.     

Sexual behavior and hormone levels during the menstrual cycles of rhesus monkeys.

The sexual interactions of 10 pairs of rhesus monkeys were observed during a control and an experimental menstrual cycle of each female. During the experimental cycle the females were treated with an antiandrogen, flutamide. Daily peripheral serum levels of estradiol, testosterone, and progesterone in each female were determined by radioimmunoassay. Sexual behavior did not correlate reliably with female serum concentrations of any hormone measured nor with the menstrual cycle stage. Administration of the antiandrogen to the females did not affect the sexual behavior of the pairs, although female serum levels of estradiol and testosterone were reduced. It was concluded that although female ovarian hormones may influence rhesus sexual interactions under some circumstances, the normal hormonal fluctuations during the menstrual cycle need not regulate this behavior; a knowledge of an intact rhesus female's hormonal condition does not allow accurate predictions about behavior displayed during laboratory pair tests with a male.     

Collective migration and cell jamming

Our traditional physical picture holds with the intuitive notion that each individual cell comprising the cellular collective senses signals or gradients and then mobilizes physical forces in response. Those forces, in turn, drive local cellular motions from which collective cellular migrations emerge. Although it does not account for spontaneous noisy fluctuations that can be quite large, the tacit assumption has been one of linear causality in which systematic local motions, on average, are the shadow of local forces, and these local forces are the shadow of the local signals. New lines of evidence now suggest a rather different physical picture in which dominant mechanical events may not be local, the cascade of mechanical causality may be not so linear, and, surprisingly, the fluctuations may not be noise as much as they are an essential feature of mechanism. Here we argue for a novel synthesis in which fluctuations and non-local cooperative events that typify the cellular collective might be illuminated by the unifying concept of cell jamming. Jamming has the potential to pull together diverse factors that are already known to contribute but previously had been considered for the most part as acting separately and independently. These include cellular crowding, intercellular force transmission, cadherin-dependent cell–cell adhesion, integrin-dependent cell–substrate adhesion, myosin-dependent motile force and contractility, actin-dependent deformability, proliferation, compression and stretch.     

Mechanisms that contribute to differences in motor performance between young and old adults.

This paper examines the physiological mechanisms responsible for differences in the amplitude of force fluctuations between young and old adults. Because muscle force is a consequence of motor unit activity, the potential mechanisms include both motor unit properties and the behavior of motor unit populations. The force fluctuations, however, depend not only on the age of the individual but also on the muscle group performing the task, the type and intensity of the muscle contraction, and the physical activity status of the individual. Computer simulations and experimental findings performed on tasks that involved single agonist and antagonist muscles suggest that differences in force fluctuations are not attributable to motor unit twitch force, motor unit number, or nonuniform activation of the agonist muscle, but that they are influenced by the variability and common modulation of motor unit discharge in both the agonist and antagonist muscles. Because the amplitude of the force fluctuations does not vary linearly with muscle activation, these results suggest that multiple mechanisms contribute to the differences in force fluctuations between young and old adults, although the boundary conditions for each mechanism remain to be determined.     

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.     

Cyclic changes in the circulating and urinary levels of ovarian steroids in the adult female owl monkey (Aotus trivirgatus).

Circulating levels of oestrone and progesterone were measured by radioimmunoassays in plasma samles from 5 female owl monkeys on 60 consecutive days. Both steroids exhibited cyclic fluctuations and based on nadir to nadir intervals the ovarian cycle was estimated to be 15.92 +/- 0.26 days. Levels of oestrone and pregnanediol-3 alpha-glucuronide were also measured in daily urine samples. The fluctuations of urinary steroids reflected those observed in plasma. Ketamine sedation had no effect on the length of the cycle. Peak values of plasma progesterone and oestrone were 250.48 +/- 11.37 and 3.59 +/- 0.066 ng/ml respectively. There was no clear hormonal distinction between the follicular and luteal phase of the cycle in these owl monkeys.     

Interstrain differences in cellular glucocorticoid reception in mice and the degree of suppression of normal killer activity during immobilization stress

The correlation between the level of stress-induced natural killer (NK) depression and glucocorticoid binding to specific spleen cell receptors and hormonal profile in inbred mouse strains (CBA, BALB/c, C57BL/c, A/Sn) has been investigated. Stable interstrain differences in stress-induced natural killer activity and glucocorticoid receptor binding (Bm and Kd) have been revealed. It was demonstrated that the mechanism of NK activity depression during stress consists in genetically determined potential sensitivity of lymphoid cells to physiological fluctuations of glucocorticoid levels. This made it possible to identify stress-resistant and stress-sensitive mouse strains.     

Estrogen- and progesterone receptors in normal cycling endometrium as studied by end-point titration

A thorough knowledge of the normal physiological fluctuations in estrogen-(ER) and progesterone receptors (PgR) is essential to characterize the changes in ER and PgR in the abnormal endometrium. We investigated the distribution of ER and PgR in frozen human cycling endometrial tissue using the commercially available ER-and PgR-ICA kits. Two-fold end-point titration (EPT) of ER and PgR antibodies was implemented to semi-quantitate more accurately ER and PgR. Semiquantitation of ER and PgR using EPT was significantly correlated to results obtained using either simple scoring or enzyme-immunoassay (EIA) methods. ER and PgR staining fluctuated in relation to the menstrual cycle. In most subphases PgR exceeded ER in both epithelial and stromal cells. Highest levels of ER and PgR were demonstrated in the glands of the functionalis in mid-to-late proliferative phases, whereas both receptors were almost undetectable by immunohistology in the glands of mid-to-late secretory phases. Endometrial stromal cells had high and nearly constant EPT values for PgR, but low values for ER througout the menstrual cycle. EPT values for ER and PgR were generally higher in the basalis than in the functionalis but showed similar cyclic fluctuations. Our results further substantiate the view that the response to hormonal stimulation is cell-type specific, and suggest differences in steroid metabolism according to cell type and layer.     

Performing Vaginal Lavage,Crystal Violet Staining,and Vaginal Cytological Evaluation for Mouse Estrous Cycle Staging Identification

A rapid means of assessing reproductive status in rodents is useful not only in the study of reproductive dysfunction but is also required for the production of new mouse models of disease and investigations into the hormonal regulation of tissue degeneration (or regeneration) following pathological challenge. The murine reproductive (or estrous) cycle is divided into 4 stages: proestrus, estrus, metestrus, and diestrus. Defined fluctuations in circulating levels of the ovarian steroids 17-β-estradiol and progesterone, the gonadotropins luteinizing and follicle stimulating hormones, and the luteotropic hormone prolactin signal transition through these reproductive stages. Changes in cell typology within the murine vaginal canal reflect these underlying endocrine events. Daily assessment of the relative ratio of nucleated epithelial cells, cornified squamous epithelial cells, and leukocytes present in vaginal smears can be used to identify murine estrous stages. The degree of invasiveness, however, employed in collecting these samples can alter reproductive status and elicit an inflammatory response that can confound cytological assessment of smears. Here, we describe a simple, non-invasive protocol that can be used to determine the stage of the estrous cycle of a female mouse without altering her reproductive cycle. We detail how to differentiate between the four stages of the estrous cycle by collection and analysis of predominant cell typology in vaginal smears and we show how these changes can be interpreted with respect to endocrine status.     

Effect of light fluctuations on photosynthesis and metabolic flux in Synechocystis sp. PCC 6803

In nature, photosynthetic organisms are exposed to fluctuating light, and their physiological systems must adapt to this fluctuation. To maintain homeostasis, these organisms have a light fluctuation photoprotective mechanism, which functions in both photosystems and metabolism. Although the photoprotective mechanisms functioning in the photosystem have been studied, it is unclear how metabolism responds to light fluctuations within a few seconds. In the present study, we investigated the metabolic response of Synechocystis sp. PCC 6803 to light fluctuations using ¹³C-metabolic flux analysis. The light intensity and duty ratio were adjusted such that the total number of photons or the light intensity during the low-light phase was equal. Light fluctuations affected cell growth and photosynthetic activity under the experimental conditions. However, metabolic flux distributions and cofactor production rates were not affected by the light fluctuations. Furthermore, the estimated ATP and NADPH production rates in the photosystems suggest that NADPH-consuming electron dissipation occurs under fluctuating light conditions. Although we focused on the water–water cycle as the electron dissipation path, no growth effect was observed in an flv3-disrupted strain under fluctuating light, suggesting that another path contributes to electron dissipation under these conditions.     

The role of Euglena gracilis paramylon in modulating xylem hormone levels,photosynthesis and water‐use efficiency in Solanum lycopersicum L

β‐1,3‐glucans such as paramylon act as elicitors in plants, modifying the hormonal levels and the physiological responses. Plant hormones affect all phases of the plant life cycle and their responses to environmental stresses, both biotic and abiotic. The aim of this study was to investigate the effects of a root treatment with Euglena gracilis paramylon on xylem hormonal levels, photosynthetic performance and dehydration stress in tomato (Solanum lycopersicum). Paramylon granules were processed to obtain the linear fibrous structures capable to interact with tomato cell membrane. Modulation of hormone levels (abscisic acid, jasmonic acid and salicylic acid) and related physiological responses such as CO₂ assimilation rate, stomatal and mesophyll conductance, intercellular CO₂ concentration, transpiration rate, water‐use efficiency, quantum yield of photosystem II and leaf water potential were investigated. The results indicate a clear dose‐dependent effect of paramylon on the hormonal content of xylem sap, photosynthetic performance and dehydration tolerance. Paramylon has the capability to enhance plant defense capacity against abiotic stress, such as drought, by modulating the conductance to CO₂ diffusion from air to the carboxylation sites and improving the water‐use efficiency.     

An ecdysteroid-induced alteration in the cell cycle of cultured Drosophila cells

The addition of physiological concentrations of the arthropod molting hormone 20-hydroxyecdysone results in the cessation of cell division in the Kc cell line of Drosophila melanogaster. Fluorometric mononitoring of the cell cycle reveals that treatment of the cells with hormone for 12 hr causes a G2 arrest. The dose-response curves are in agreement with those obtained for other hormonal effects in both the Kc line and the intact animal. In the continual presence of hormone, cells remain G2-arrested for approximately 100 hr, resuming division by 120 hr. Cells which have responded once to ecdysteroids and subsequently reentered the cell cycle are insensitive to hormonal restimulation. This lack of response has been correlated with, and is probably due to, the loss of ecdysteroid receptors in stimulated cells.