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.     

Sexual behavior and urinary ovarian hormone concentrations during the lowland Gorilla menstrual cycle

Sexual behaviors were recorded and urinary concentrations of total estrogens and pregnanediol-3-glucuronide (Pdg) measured during six normal menstrual cycles from two female lowland gorillas in a stable, captive group. Frequencies of female presentations, mounts, and copulations were positively associated with peak estrogen values but not with elevations of Pdg. These results support the observation that sexual behaviors in the gorilla occur most frequently in the periovulatory period and that copulations serve primarily a sexual function.     

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.     

Changes in brain size during the menstrual cycle

Background

There is increasing evidence for hormone-dependent modification of function and behavior during the menstrual cycle, but little is known about associated short-term structural alterations of the brain. Preliminary studies suggest that a hormone-dependent decline in brain volume occurs in postmenopausal, or women receiving antiestrogens, long term. Advances in serial MR-volumetry have allowed for the accurate detection of small volume changes of the brain. Recently, activity-induced short-term structural plasticity of the brain was demonstrated, challenging the view that the brain is as rigid as formerly believed.

Methodology/Principal Findings

We used MR-volumetry to investigate short-term brain volume changes across the menstrual cycle in women or a parallel 4 week period in men, respectively. We found a significant grey matter volume peak and CSF loss at the time of ovulation in females. This volume peak did not correlate with estradiol or progesterone hormone levels. Men did not show any significant brain volume alterations.

Conclusions/Significance

These data give evidence of short-term hormone-dependent structural brain changes during the menstrual cycle, which need to be correlated with functional states and have to be considered in structure-associated functional brain research.     

Localization of ubiquitin and ubiquitin cross-reactive protein in human and baboon endometrium and decidua during the menstrual cycle and early pregnancy

We have examined the distribution of ubiquitin and the related ubiquitin cross-reactive protein (UCRP) in paraffin-embedded sections of human and baboon endometrium and decidua by immunoperoxidase or immunofluorescence cytochemistry with antibodies raised against ubiquitin, UCRP, CD45, and insulin-like growth factor-binding protein-1. Anti-ubiquitin immunoreactivity was present in the nonpregnant endometrium, particularly in the glandular epithelial cells, and up-regulated in endometrial stromal cells as they decidualized at the beginning of pregnancy. Anti-UCRP immunoreactivity was absent from nonpregnant tissue but accumulated to high levels in decidual cells during pregnancy. Western blotting indicated that immunoreactivity was primarily due to the presence of ubiquitin and UCRP conjugated to other proteins, and that although levels of ubiquitin-protein conjugates do not change substantially during pregnancy, decidualization is accompanied by the appearance of conjugates of UCRP. Baboon uterine tissues demonstrated a similar distribution of the two proteins, which indicates that the baboon may be a useful model for study of the role of the ubiquitin system and UCRP in the establishment of pregnancy in humans.     

Control of sweating during the human menstrual cycle

Thermoregulatory responses were studied in seven women during two separate experimental protocols in the follicular (F, days 4-7) phase and during the luteal (L, days 19-22) phase of the menstrual cycle. Continuous measurements of esophageal temperature (Tes), mean skin temperature (Tsk), oxygen uptake and forearm sweating (ms) were made during all experiments. Protocol I involved both passive heat exposure (3 h) and cycle exercise at approximately 80% VO2 peak during which the environmental chamber was controlled at Ta = 50.0 degrees C, rh = 14% (Pw = 1.7 kPa). In protocol II subjects were tested during thirty-five minutes of exercise at approximately 85% VO2 peak at Ta = 35 degrees C and rh = 25% (Pw = 1.4 kPa). The normal L increase in resting Tes (approximately 0.3 degrees C) occurred in all seven subjects. Tsk was higher during L than F in all experiments conducted at 50 degrees C. During exercise and passive heat exposure, the Tes threshold for sweating was higher in L, with no change in the thermosensitivity (slope) of ms to Tes between menstrual cycle phases. This rightward or upward shift in Tes threshold for initiation of sweating averaged 0.5 degrees C for all experiments. The data indicate the luteal phase modulation in the control of sweating in healthy women is also apparent during severe exercise and/or heat stress.     

Changes in plasma adrenomedullin levels during the menstrual cycle

We investigated whether the levels of adrenomedullin, a novel peptide produced by several tissues, including the pituitary gland, change during the ovarian cycle. We studied 13 healthy women with regular menstrual cycles. Plasma samples were collected at 7, 14, 21 and 28 days of the ovarian cycle and assayed for adrenomedullin 1-52 using a specific RIA. LH, FSH, 17beta-estradiol, and progesterone concentrations were also determined. The adrenomedullin profile during ovarian cycle was similar to that of LH; plasma adrenomedullin increased from 10.9 pg/ml at the 7th day to 15.1 pg/ml at the 14th, and decreased to 8.5 pg/ml in the subsequent menses. The changes in plasma adrenomedullin were related to changes in LH and 17beta-estradiol. The cause of the increase in adrenomedullin levels during the late follicular phase of the menstrual cycle is not clear. Since it has been demonstrated that adrenomedullin is involved in the regulation of hypothalamus-pituitary-adrenal gland and its secretion is regulated by sex hormones we speculate that adrenomedullin could also play a role in regulating the hypothalamus-pituitary-ovary feedback. Alternatively it may be involved in the regulation of fluid and electrolyte homeostasis during the menstrual cycle.     

Plasma alpha-melanocyte-stimulating hormone during the menstrual cycle in women

alpha-Melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) immunoreactivity (IR) was measured in the blood of 22 healthy women with normal ovulatory process in the early and late follicular (near to ovulation) phases and in the early luteal phase of the menstrual cycle. Plasma alpha-MSH IR ranged from undetectable values to 81.3 pg/ml, the highest levels being found in the late follicular phase (15.52 +/- 4.16 pg/ml). In contrast, plasma ACTH IR was always detectable (range: 18.5-63.2 pg/ml), but its concentration did not differ significantly between the 3 phases of the menstrual cycle. High-pressure liquid chromatography fractionation of Sep pak C18-purified alpha-MSH IR revealed in all 3 phases the presence of 3 major peaks of alpha-MSH IR, coeluting with desacetyl-alpha-MSH, alpha-MSH and diacetyl-alpha-MSH, respectively. The most abundant peak always coeluted with authentic desacetyl-alpha-MSH, and the ratio between this deacetylated and the other 2 acetylated forms was similar in the 2 follicular phases (1:1.25 and 1:1.16 in the early and late phase, respectively), but significantly different in the luteal phase (1:0.48). The fluctuations in plasma concentration of the above MSH-related peptides suggest that different rates of alpha-MSH acetylation and release take place in the pituitary gland depending on the phase of the menstrual cycle.     

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.