Serum levels of gonadotropins and gonadal steroids,including testosterone,during the menstrual cycle of the chimpanzee (Pan troglodytes)

The objective of this study was to expand the data on menstrual cycle serum hormone patterns in female common chimpanzees, both in terms of the number of cycles analyzed and by the addition of data on testosterone levels. Samples were obtained from 11 unanesthetized animals trained for conscious blood withdrawal. LH, FSH, 17β-estradiol (E₂), progesterone (P), and testosterone (T) were measured by radioimmunoassay, genital swelling was recorded, and menstrual blood was noted. Concurrent midcycle elevations in LH and FSH and luteal phase elevations in progesterone suggested that the cycles were ovulatory. Detumescence of genital swelling occurred about 3 days after the midcycle LH peak, 1 day after the luteal phase nadir in E₂, and 1 day after P levels exceeded 5 ng/ml. These relationships provide further support for the use of genital swelling in monitoring progress of the menstrual cycle. The hormone patterns in the chimpanzees closely resembled those of the human females, but E₂ and T levels were higher. The levels of E₂ and T were higher and the midcycle elevation in T was broader in the chimpanzee than in gorillas and orangutans. This is of interest because E₂ and T are implicated in the regulation of mating, and chimpanzees mate over a greater portion of the cycle than the other apes. These data indicate the need for further study of hormonal contributions to the different patterns of mating in the great apes. They also support the use of the female common chimpanzee as a model for the human female in endocrine studies of the menstrual cycle.     

Cyclical changes in the renin-angiotensin-aldosterone system during the menstrual cycle of the baboon (Papio hamadryas)

Abstract: This study characterizes the renin-angiotensin-aldosterone system during the normal menstrual cycle in the baboon. Ten animals received a daily dose of an ACE inhibitor or placebo in a randomized blind cross-over design. Data were obtained during the mid-follicular and early luteal phases of normal non-pregnant menstrual cycles. All examinations and blood collections were performed with ketamine sedation: 7–kg by im injection. Blood pressure was recorded by sphygmomanometer. Serum ACE activity was measured by spectrophotometry. Aldosterone (ALDO), angiotensin I (AI), and angiotensin II (AII) were measured by radioimmunoassay. Plasma renin activity (PRA) was measured by AI generation. The renin-angiotensin-aldosterone system was found to be activated in the follicular phase and suppressed during the luteal phase of the normal non-pregnant menstrual cycle in the baboon.     

The influence of hormonal changes during menstrual cycle on serum adiponectin concentrations in healthy women

Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.     

CO2 sensitivity changes during the menstrual cycle

A study of the changes in CO2 sensitivity at rest was undertaken in 20 regularly menstruating females in an attempt to determine the influence of the menstrual cycle on this variable. A biphasic oral temperature graph was used to signify fertility and demarcate three phases of the cycle. A CO2-rebreathing test was conducted 3 times/wk for 6 wk to obtain CO2 sensitivity and CO2 threshold measures. An analysis of variance was used to compare the results collected in each phase of the cycle for each of the variables. A significant increase was found in the sensitivity to CO2 between the follicular and luteal phases, a significant decrease between the luteal and menstrual phases, and no significant difference between the follicular and menstrual phases. The change between follicular and luteal phases was attributed to the effect of progesterone, which is elevated during the luteal phase. No significant change was found in the CO2 threshold level.     

Hormone changes during the menstrual cycle of Chinese women

The concentrations of LH, FSH, prolactin, oestradiol and progesterone in serum were measured daily during the menstrual cycle of 100 normal Chinese women. The cyclic changes in LH, FSH, oestradiol and progesterone were typical of ovulatory cycles in women of other ethnic groups as reported in the literature. The geometric mean of the LH midcycle peak value was 51 X 64 i.u./l, the FSH mid-cycle peak value was 11 X 52 i.u./l, the preovulatory oestradiol peak was 1229 X 12 pmol/l, and the progesterone luteal maximum was 53 X 27 nmol/l. The cyclic changes of prolactin concentrations were irregular: the value at mid-cycle was significantly higher than that at the follicular or luteal phases. A correlation between the length of the cycle and mean concentrations of LH and oestradiol at different stages throughout the cycle was shown.     

Perceptual-motor performance during the menstrual cycle

Study I: Choice reaction times were measured in 12 normally menstruating women using a numerals-keys serial response task with three set sizes (two, four, and eight). Testing was carried out at four successive phases of the menstrual cycle corresponding with different states of neuroendocrine activity. They were, respectively: (i) 2nd day of flow; (ii) 4th day after cessation of flow (preovulation); (iii) 12th day after flow (postovulation); and (iv) 3rd day before next (estimated) flow. No consistent relationship between performance and phase of the cycle could be demonstrated. The only significant effect was an increase in reaction time with increasing set size. The study provides no support for the theory that variations in estrogen and progesterone levels may cause behaviorally relevant changes in central nervous system functioning. Study II: Four women suffering from premenstrual tension were examined thrice weekly on the same task for 4 consecutive weeks. Three hours prior to testing, a blood sample was drawn and assayed for estrogen, progesterone, and gonadotropin (LH). Performance on the serial choice response task bore no consistent relationship to blood levels of any of the three hormones. Performance before ovulation (as determined by peak LH level) did not differ significantly from that after ovulation. These results concur with those of Study I: there was no reliable relationship between hormonal status and performance.     

Fertility in the male gorilla (Gorilla gorilla): Relationship to semen parameters and serum hormones

Circulating levels of steroid and protein hormones were measured in 17 adult male lowland gorillas (Gorilla gorilla). The population included both fertile and infertile males as identified by previous siring of offspring and presence or absence of spermatozoa in the ejaculate obtained by rectal probe electrostimulation. Correlations were sought between levels of testosterone, dihydrotestosterone, androstenedione, estrone, estradiol, progesterone, 170H-progesterone, dihydroepiandrosterone, luteinizing hormone, follicle-stimulating hormone (FSH), and potential fertility status. The results identify normal circulating levels of these hormones, and indicate that aspermatogenesis and infertility are not necessarily associated with any alteration in levels of gonadal steroids. There is an association of aspermatogenesis with elevation of FSH. Levels of adrenal androgens are more similar to other non-human primates than to the human, which is of interest because in other aspects of reproductive physiology so far investigated the gorilla has proved to resemble the human more closely than it does the other nonhuman primates.     

Cyclic changes in phospholipid content and composition in human endometrium during the menstrual cycle

A significant increase in total phospholipid content of the endometrium took place during the secretory phase of the human menstrual cycle (26% increase from mid-proliferative to premenstrual stage). The major phospholipid, phosphatidylcholine, was increased by 30%, whereas phosphatidylethanolamine was unchanged. Phosphatidyl-serine and -inositol underwent the largest percentage increases (40%). Phosphatidic acid levels were the only ones to decrease (-52%), a finding consistent with the role of this lipid as precursor of the increased phospholipids. The changes did not markedly affect phospholipid composition, except for a significant decrease in the proportions of phosphatidate and phosphatidylethanolamine. Arachidonate and eicosatrienoate (n-6) were the major polyunsaturated fatty acids. C22 tetra-, penta- and hexa-enoic fatty acids of the n-3 and n-4 families were also present in all major endometrial glycerophospholipids throughout the cycle. The mass changes in phospholipids during the cycle occurred without alteration of their fatty acid composition.     

One-carbon metabolism during the menstrual cycle and pregnancy

Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B₁₂, vitamin B₆, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.     

Bifurcation analysis of a model for hormonal regulation of the menstrual cycle

A model for hormonal control of the menstrual cycle with 13 ordinary differential equations and 41 parameters is presented. Important changes in model behavior result from variations in two of the most sensitive parameters. One parameter represents the level of estradiol sufficient for significant synthesis of luteinizing hormone, which causes ovulation. By studying bifurcation diagrams in this parameter, an interval of parameter values is observed for which a unique stable periodic solution exists and it represent an ovulatory cycle. The other parameter measures mass transfer between the first two stages of ovarian development and is indicative of healthy follicular growth. Changes in this parameter affect the uniqueness interval defined with respect to the first parameter. Hopf, saddle-node and transcritical bifurcations are examined. To attain a normal ovulatory menstrual cycle in this model, a balance must be maintained between healthy development of the follicles and flexibility in estradiol levels needed to produce the surge in luteinizing hormone.