scholarly journals Regulation of the cGMP-cPKG pathway and large-conductance Ca2+-activated K+ channels in uterine arteries during the ovine ovarian cycle

2010 ◽  
Vol 298 (2) ◽  
pp. E222-E228 ◽  
Author(s):  
Liaqat H. Khan ◽  
Charles R. Rosenfeld ◽  
Xiao-tie Liu ◽  
Ronald R. Magness

The follicular phase of the ovine ovarian cycle demonstrates parallel increases in ovarian estrogens and uterine blood flow (UBF). Although estrogen and nitric oxide contribute to the rise in UBF, the signaling pathway remains unclear. We examined the relationship between the rise in UBF during the ovarian cycle of nonpregnant sheep and changes in the uterine vascular cGMP-dependent pathway and large-conductance Ca2+-activated K+ channels (BKCa). Nonpregnant ewes ( n = 19) were synchronized to either follicular or luteal phase using a vaginal progesterone-releasing device (CIDR), followed by intramuscular PGF2α, CIDR removal, and treatment with pregnant mare serum gonadotropin. UBF was measured with flow probes before tissue collection, and second-generation uterine artery segments were collected from nine follicular and seven luteal phase ewes. The pore-forming α- and regulatory β-subunits that constitute the BKCa, soluble guanylyl cyclase (sGC), and cGMP-dependent protein kinase G (cPKG) isoforms (cPKG1α and cPKG1β) were measured by Western analysis and cGMP levels by RIA. BKCa subunits were localized by immunohistochemistry. UBF rose >3-fold ( P < 0.04) in follicular phase ewes, paralleling a 2.3-fold rise in smooth muscle cGMP and 32% increase in cPKG1α ( P < 0.05). sGC, cPKG1β, and the BKCa α-subunit were unchanged. Notably, expression of β1- and β2-regulatory subunits rose 51 and 79% ( P ≤ 0.05), respectively. Increases in endogenous ovarian estrogens in follicular-phase ewes result in increases in UBF associated with upregulation of the cGMP- and cPKG-dependent pathway and increased vascular BKCa β/α-subunit stoichiometry, suggesting enhanced BKCa activation contributes to the follicular phase rise in UBF.

1991 ◽  
Vol 260 (3) ◽  
pp. E464-E470 ◽  
Author(s):  
R. R. Magness ◽  
C. R. Rosenfeld ◽  
B. R. Carr

Elevated uterine blood flow is associated with increases in local estrogen-to-progesterone ratios during the follicular phase of the ovarian cycle and late pregnancy. Because protein kinase C (PKC) activation increases arterial tone, decreased PKC activity may mediate vasodilation. Therefore, we determined uterine (UA) and systemic artery (SA, omental) PKC activity (pmol.mg protein-1.min-1) during the follicular (n = 6), early luteal (n = 4), and late luteal (n = 3) phases of the sheep ovarian cycle, and at 110 +/- 3 (n = 4) and 130 +/- 1 (n = 8) (+/- SE) days of ovine gestation. The stage of the ovarian cycle was verified by the presence of follicles (high estrogen) or corpora lutea (high progesterone) on the ovary and by plasma estrogen and progesterone concentrations. UA-PKC activity (pmol.mg protein-1.min-1) during the follicular phase was 100 +/- 18 and increased progressively to 155 +/- 28 during the early luteal phase and to 219 +/- 37 (P less than 0.05) during the late luteal phase; SA-PKC activity was unchanged. A local utero-ovarian relationship was observed, i.e., UA-PKC activity was lower (P less than 0.001) in UA ipsilateral to ovaries with only follicles (105 +/- 14) when compared with UA adjacent to ovaries with corpora lutea (224 +/- 26), which was similar to SA-PKC activity (184 +/- 35). UA-PKC activity fell from 344 +/- 70 at 110 days to 109 +/- 12 at 130 days gestation (P less than 0.05); SA-PKC activity was unchanged. During the ovarian cycle and latter one-third of ovine pregnancy, increased estrogen production is associated with decreased UA-PKC activity; thus local ovarian and placental steroids may alter PKC activity, thereby regulating UA tone and blood flow.


2002 ◽  
pp. 347-356 ◽  
Author(s):  
AD Genazzani ◽  
M Luisi ◽  
B Malavasi ◽  
C Strucchi ◽  
S Luisi ◽  
...  

OBJECTIVE: To investigate whether allopregnanolone, a neuroactive steroid involved in modulating behavioural and neuroendocrine functions, shows episodic secretion in eumenorrheic women, during the follicular and luteal phases of the menstrual cycle, and in women with stress-induced amenorrhea. PATIENTS: Six eumenorrheic women and 14 women with hypothalamic amenorrhea were enrolled for the present study. METHODS: All subjects underwent hormonal evaluation in baseline conditions and a pulsatility study to determine LH, cortisol and allopregnanolone episodic release. Eumenorrheic subjects were investigated twice, in the follicular phase (days 3-7) and in the luteal phase (days 18-22) of the menstrual cycle. LH, FSH, prolactin, estradiol, phosphate, DHEA, allopregnanolone and cortisol levels were evaluated in each case. RESULTS: In healthy women, serum gonadotropin and gonadal steroid levels were significantly lower (P<0.01 and P<0.05 respectively) than those in amenorrheic subjects. Allopregnanolone was higher in amenorrheic subjects and during the luteal phase, compared with the follicular phase, of eumenorrheic subjects (P<0.01). Pulse analysis revealed a significant episodic discharge of allopregnanolone in all subjects (follicular phase 6.5+/-0.3 peaks/6 h and luteal phase 5.5+/-0.4 peaks/6 h, hypothalamic amenorrhea 7.0+/-0.7 peaks/6 h) with higher pulse amplitude in amenorrheic subjects and during the luteal phase compared with the follicular phase of the eumenorrheic subjects (P<0.05). Moreover, the specific concordance index demonstrated that allopregnanolone is coupled with LH only during the luteal phase of the cycle and with cortisol during both phases. Allopregnanolone-cortisol coupling was also observed in amenorrheic subjects. CONCLUSIONS: Allopregnanolone is secreted episodically. Both the ovary and adrenal glands release this steroid hormone and it shows temporal coupling with LH only during the luteal phase, with cortisol during both the studied phases of the menstrual cycle in eumenorrheic women and again with cortisol in hypothalamic amenorrheic patients.


1989 ◽  
Vol 120 (1) ◽  
pp. 59-65 ◽  
Author(s):  
J. K. Findlay ◽  
B. Doughton ◽  
D. M. Robertson ◽  
R. G. Forage

ABSTRACT Immunization of ewes against a pure recombinant preparation of the α subunit of bovine inhibin (α-bI) resulted in a three- to fourfold increase in ovulation rate, associated with antibodies in plasma recognizing pure native 31 kDa inhibin. The aim of this study was to examine the effects of this immunization on basal and GnRH-stimulated plasma concentrations of FSH and LH in ewes during the anoestrous and breeding seasons. The groups were untreated control ewes (n = 5), control ewes treated with keyhole limpet haemocyanin (KLH alone, n = 4), ewes treated with α-bI alone (n = 4) and α-bI–KLH conjugate-treated ewes (n = 3). There were no effects of immunization on basal FSH or LH in anoestrous ewes, despite the presence of antibodies recognizing 31 kDa inhibin. In the breeding season, immunization against α-bI resulted in increased basal (follicular phase, P < 0·1; luteal phase P < 0·05) and GnRH-stimulated (follicular phase only, P < 0·001) release of FSH, but not LH. The data are compatible with the hypotheses that the increase in ovulation rate in immunized ewes is due to an increase in circulating FSH concentrations and that inhibin may only have a major peripheral influence on FSH in sheep during the breeding season. Journal of Endocrinology (1989) 120, 59–65


2015 ◽  
Vol 15 (1) ◽  
pp. 107-117 ◽  
Author(s):  
Piotr Brodzki ◽  
Adam Brodzki ◽  
Łukasz Kurek ◽  
Jan Marczuk ◽  
Marcin R. Tatara

Abstract The aim of the study was to examine cytological changes in the uterus in cows during the follicular and luteal phases of the ovarian cycle, as well as to compare two different methods (brush and flushing) used for cytological material collection and to evaluate their usefulness for monitoring of the endometrium. Ovarian cycle phases were confirmed by ultrasound and by the level of sex hormones (17-β-estradiol and progesterone). The following types of cells were identified in the cytological smears: type I - surface cells; type II - intermediate cells; type III - basal cells; polymorphonuclear leukocytes (PMNs); L - lymphocytes. The number of type I and III cells was statistically significantly higher in the follicular phase than in the luteal phase, both in smears prepared using a brush (P<0.001) and by uterine flush (P=0.003). The number of type II cells was statistically significantly higher in the luteal phase than in the follicular phase in both methods (P<0.001). The results of the study show that phases of the ovarian cycle in cows can be identified based on changes in the quality and percentage of different types of endometrial cells in a cytological examination.


1984 ◽  
Vol 102 (1) ◽  
pp. 19-26 ◽  
Author(s):  
S.-A. K. Eastman ◽  
D. W. Makawiti ◽  
W. P. Collins ◽  
J. K. Hodges

ABSTRACT Non-invasive methods for monitoring reproductive status based on the measurement of urinary steroid conjugates were examined. Levels of urinary oestrone-3-glucuronide, oestrone-3-sulphate, oestradiol glucuronide, oestradiol sulphate and pregnanediol-3α-glucuronide were determined during the ovarian cycle and pregnancy. Sequential hydrolysis showed oestradiol conjugates to be more abundant than oestrone conjugates. The levels of sulphates and glucuronides were similar in the follicular phase whereas sulphates predominated during the luteal phase and pregnancy. Although levels of oestrone-3-sulphate were two- to fourfold lower than those of oestradiol sulphate, measured after hydrolysis, the profiles throughout the cycle and pregnancy were similar. Levels of oestrone-3-sulphate, measured by direct assay, were below 1 μmol/mmol creatinine during the follicular phase, rising 3–4 days after ovulation to reach maximum values (2–8 μmol/mmol creatinine) in the mid-luteal phase. There was no consistent increase before ovulation. Levels during pregnancy rose gradually until days 70–90, after which there was no further increase (gestation length = 144 days). The pattern of pregnanediol-3α-glucuronide was similar to that of oestrone-3-sulphate during the ovarian cycle but levels did not increase during pregnancy. The patterns of excretion of oestrogen and progesterone metabolites were similar to the pattern of the circulating hormones during the ovarian cycle. Circulating and urinary hormone patterns were similar for oestrogens throughout pregnancy but pregnanediol-3α-glucuronide did not reflect progesterone secretion beyond day 70 of gestation. J. Endocr. (1984) 102, 19–26


Author(s):  
Shehnaz Shaikh

Introduction: Menstrual cycle or menstruation involved discharge of sanguinous fluid and a sloughing of uterine wall. In women menstruation occurs at regular intervals on an average of 28 days, although most women gave a history of regular intervals of 28 to 30 days. About 10% -15% of women showed cycle at the precise 28 ± 2 days intervals when menstrual calendar was utilized. Normally in young women in different phases of ovarian cycles the plasma levels of estrogen vary. Ovulation occurs in the first 12-13th day of menstrual cycle, which is termed estrogen surge and second occurs in mid-luteal phase. During mid cycle or follicular phase of menstrual cycle the plasma concentration of progesterone is very low about 0.9 ng/mL. its level starts rising owing to secretion from the granulose cells. During luteal phase progesterone level reaches its peak value of 18 ng/mL and its level fall to a minimum value toward the end of the cycle. Estrogen affects local and systemic vasodilation. The menstrual cycle envelops two fundamental stages, the follicular stage (FP) and the luteal stage (LP). The follicular stage can part advance into two substages; the early FP, which is characterised with moo concentrations of both the key hormones estrogen and progesterone; and the mid FP where estrogen is tall autonomously from progesterone. The LP is epitomized by tall concentration of both estrogen and progesterone. These two fundamental stages are isolated by a soak surge in luteinizing hormone activating ovulation. These recurrent changes are said to be frequency unsurprising while long time. Aim: The main aim of this study is to evaluate the Cardiorespiratory functions changes during different Phases of Menstrual Cycle.   Material and methods: In this study, 20 with normal weight, 20 with obese and 20 with overage were included and taken them as a sample size. In this study all the young women those were recruited as a sample size are unmarried, undergraduate female student with the between the age group of 18-22years, having regular 28+6 days menstrual cycle for at least last 6months prior to this study. For the collection of data all the participants were instructed to attend the physiology lab department during each of three different phases. Day-2 during menstrual phase, Day-7, during follicular phase and Day-22 during luteal phase and the following parameters were recorded as Anthropometric measurements, measuring of pulse rate and blood pressure and cardiac efficiency test. Result: In general, work out proficiency changed essentially amid the distinctive stages of the menstrual cycle with the most elevated amid luteal stage and least amid menstrualo stage. There was no critical contrast in impact test amid menstrual stage, follicular stage and luteal stage of menstrual cycle among three bunches of people. Conclusion: We have watched noteworthy increment in cardiac and respiratory proficiency within the luteal stage of the menstrual cycle in ordinary weight people. Lower wellness levels were watched in overweight and stout females. In this manner hone of customary work out and admissions of solid slim down which offer assistance in lessening the weight and in turn the BMI will offer assistance in improving the physical wellness of the people. Keywords: Cardiorespiratory, Menstrual cycle, expiratory blast test


1979 ◽  
Vol 90 (2) ◽  
pp. 372-384 ◽  
Author(s):  
N. P. Goncharov ◽  
A. G. Taranov ◽  
A. V. Antonichev ◽  
V. M. Gorlushkin ◽  
T. Aso ◽  
...  

ABSTRACT Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20α-dihydroprogesterone, oestrone, oestradiol) or competitive protein binding (cortisol) techniques. The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20α-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration > 24 h) of oestradiol and oestrone concentrations during the follicular phase. It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females the inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.


Author(s):  
Hannah N. Willett ◽  
Kristen J. Koltun ◽  
Anthony C. Hackney

This study examined the effect of estradiol-β-17 across the menstrual cycle (MC) during aerobic exercise on energy substrate utilization and oxidation. Thirty-two eumenorrheic (age = 22.4 ± 3.8 y (mean ± SD)), physically active women participated in two steady-state running sessions at 65% of VO2max, one during the early follicular and one during the luteal phase of the MC. Blood samples were collected at rest before each exercise session and analyzed for Estradiol-β-17 to confirm the MC phase. Carbohydrate (CHO) utilization and oxidation values were significantly lower (p < 0.05) in the luteal (utilization: 51.6 ± 16.7%; oxidation: 1.22 ± 0.56 g/min; effect size (ES) = 0.45, 0.27) than follicular phase (utilization: 58.2 ± 15.1%; oxidation: 1.38 ± 0.60 g/min) exercise sessions. Conversely, fat utilization and oxidation values were significantly (p < 0.05) higher in the luteal (utilization: 48.4 ± 16.7%; oxidation: 0.49 ± 0.19 g/min; ES = 0.45,0.28) than follicular phase (utilization: 41.8 ± 15.1%; oxidation: 0.41 ± 0.14 g/min). Estradiol-β-17 concentrations were significantly (p < 0.01) greater during the luteal (518.5 ± 285.4 pmol/L; ES = 0.75) than follicular phase (243.8 ± 143.2 pmol/L). Results suggest a greater use of fat and reduced amount of CHO usage during the luteal versus follicular phase, directly related to the change in resting estradiol-β-17. Future research should investigate the role these changes may play in female athletic performance.


Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 591-600
Author(s):  
Kiminori Shimizu ◽  
Nancy P Keller

Abstract In the filamentous fungus Aspergillus nidulans, a heterotrimeric G protein α-subunit and an RGS domain protein, encoded by fadA and flbA, respectively, regulate production of the carcinogenic metabolite sterigmatocystin (ST) and asexual spores (i.e., conidia). We investigated the genetic involvement of the cAMP-dependent protein kinase catalytic subunit (PkaA), a potential downstream target of FadA activity, in ST production and conidiation. Relative to wild type, sporulation was decreased in the pkaA overexpression strain but was not totally absent, as occurs in ΔflbA or fadAG42R (fadA-dominant active) strains. Deletion of pkaA resulted in a hyper-conidiating strain with limited radial growth. This phenotype was epistatic to mutation in flbA or fadA; the double mutants ΔpkaA; ΔflbA and ΔpkaA; fadAG42R recovered sporulation and their radial growth was severely restricted. PkaA overexpression also negatively regulated AflR, the ST biosynthesis-specific transcription factor, both transcriptionally and post-transcriptionally. Deletion of pkaA restored ST production in the ΔflbA background but not in the fadAG42R background. These data provide genetic evidence that the FlbA/FadA signaling pathway regulating ST production and morphological development is partially mediated through PkaA.


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