Altered Serotonergic Activity in Women with Dysphoric Premenstrual Syndromes

1993 ◽  
Vol 23 (1) ◽  
pp. 1-27 ◽  
Author(s):  
Uriel Halbreich ◽  
Henry Tworek
Keyword(s):  
Treatment Outcome ◽  
Menstrual Cycle ◽  
Luteal Phase ◽  
Symptomatic Treatment ◽  
Gonadal Hormones ◽  
Interactive System ◽  
Library Search ◽  
Serotonergic Activity ◽  
Late Luteal Phase

Objective: Dysphoric Premenstrual Syndromes (PMS) are quite prevalent and in some women they are severe enough to warrant treatment. Their pathophysiology is still unknown, despite increased interest and research. Here we review the possible role of serotonin in the multidimensional interactive pathophysiology of PMS. Method: Over 170 articles are reviewed. An extensive library search has been conducted and articles are included because of their relevance to: 1) the phenomenology of PMS; 2) the putative association of serotonergic (5-HT) activity with syndromes that occur premenstrually; 3) changes in 5-HT activity along the menstrual cycle, especially the late luteal phase; 4) influence of gonadal hormones on serotonergic functions; 5) endocrine strategies for assessment of 5-HT abnormalities; and 6) treatment studies of PMS with serotonergic agonists. Results and Conclusions: The data presented here suggest that post-synaptic serotonergic responsivity might be altered during the late-luteal-premenstrual phase of the menstrual cycle. Some serotonergic functions of women with PMS might be altered during the entire cycle and be associated with a vulnerability trait. It is hypothesized that gonadal hormones might cause changes in levels of activity of 5-HT systems as part of a multidimensional interactive system. Strategies to evaluate 5-HT activities in the context of the menstrual cycle are discussed—leading to the conclusion that the most promising approach is active stimulation with specific post-synaptic serotonin agonists. Treatment outcome studies of some imperfect compounds that are currently applied as a symptomatic treatment of PMS support the notion that 5-HT is involved in the pathophysiology of these syndromes.

Manipulation of inhibin during the luteal-follicular phase transition of the primate menstrual cycle fails to affect FSH secretion

1994 ◽  
Vol 142 (1) ◽  
pp. 181-186 ◽  
Author(s):  
H M Fraser ◽  
C G Tsonis
Keyword(s):  
Phase Transition ◽  
Menstrual Cycle ◽  
Luteal Phase ◽  
Elevated Serum ◽  
Follicular Phase ◽  
Serum Concentrations ◽  
Late Luteal Phase ◽  
Early Follicular Phase ◽  
Negative Feedback Control

Abstract The pattern of inhibin concentrations in blood during the menstrual cycle in primates has suggested an endocrine role of inhibin in the negative feedback control of FSH secretion during the luteal phase. Conversely, the fall in inhibin during the late luteal phase may play a role in the rise in serum FSH during the luteal-follicular phase transition. This hypothesis was examined by determining the effects of manipulation of inhibin on FSH secretion in stumptailed macaques. During the mid-luteal phase the putative inhibin feedback was inhibited by i.v. administration of 20 ml of ovine antiserum to human recombinant inhibin in 4 macaques. FSH secretion was unaffected during the initial 24 h period post-treatment and the timing of the rise in FSH which occurred during the subsequent luteal-follicular phase transition was normal. To determine whether the elevated serum concentrations of FSH observed during the early follicular phase could be reduced by administration of inhibin, 5 cyclic macaques were treated with 200 μg of recombinant human inhibin i.v. Serum FSH concentrations were unaltered. These results suggest that inhibin does not play a major role in modulating FSH secretion during the luteal-follicular phase transition. Journal of Endocrinology (1994) 142, 181–186

scholarly journals Human chorionic gonadotropin-induced amphiregulin stimulates aromatase expression in human granulosa-lutein cells: a mechanism for estradiol production in the luteal phase

2019 ◽  
Vol 34 (10) ◽  
pp. 2018-2026 ◽  
Author(s):  
Lanlan Fang ◽  
Yiping Yu ◽  
Yiran Li ◽  
Sijia Wang ◽  
Ruizhe Zhang ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Follicular Fluid ◽  
Natural Science ◽  
Luteal Phase ◽  
Small Sample ◽  
Luteal Cell ◽  
Aromatase Expression ◽  
Protein Levels

Abstract STUDY QUESTION Does amphiregulin (AREG), the most abundant and important epidermal growth factor receptor (EGFR) ligand in the follicular fluid, regulate aromatase expression in human granulosa-lutein (hGL) cells? SUMMARY ANSWER AREG mediates the hCG-induced up-regulation of aromatase expression and estradiol (E2) production in hGL cells. WHAT IS KNOWN ALREADY AREG expression and secretion are rapidly induced by hCG in hGL cells and mediate physiological functions of LH/hCG in the ovary. EGFR protein is expressed in follicles not only in the pre-ovulatory phase but also throughout the luteal phase of the menstrual cycle. After the LH surge, the human corpus luteum secretes high levels of E2, which regulates various luteal cell functions. Aromatase is an enzyme responsible for a key step in the biosynthesis of E2. However, whether AREG regulates aromatase expression and E2 production in hGL cells remains unexplored. STUDY DESIGN, SIZE, DURATION This study is an experimental study performed over a 1-year period. In vitro investigations examined the role of AREG in the regulation of aromatase expression and E2 production in primary hGL cells. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary hGL cells were obtained from women undergoing IVF treatment in an academic research center. Aromatase mRNA and protein levels were examined after exposure of hGL cells to recombinant human AREG, hCG or LH. The EGFR tyrosine kinase inhibitor AG1478, PI3K inhibitor LY294002 and siRNAs targeting EGFR, LH receptor, StAR and AREG were used to verify the specificity of the effects and to investigate the underlying molecular mechanisms. Reverse transcription quantitative real-time PCR (RT-qPCR) and western blot were used to measure the specific mRNA and protein levels, respectively. Follicular fluid and serum were collected from 65 infertile women during IVF treatment. Pearson’s correlation analysis was performed to examine the correlation coefficient between two values. MAIN RESULTS AND THE ROLE OF CHANCE Treatment of hGL cells with AREG-stimulated aromatase expression and E2 production. Using pharmacological inhibitors and specific siRNAs, we revealed that AREG-stimulated aromatase expression and E2 production via EGFR-mediated activation of the protein kinase B (AKT) signaling pathway. In addition, inhibition of EGFR activity and AREG knockdown attenuated hCG-induced up-regulation of aromatase expression and E2 production. Importantly, the protein levels of AREG in the follicular fluid were positively correlated with the E2 levels in serum after 2 days of oocyte pick-up and in the follicular fluid of IVF patients. LARGE-SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The in vitro setting of this study is a limitation that may not reflect the real intra-ovarian microenvironment. Clinical data were obtained from a small sample size. WIDER IMPLICATIONS OF THE FINDINGS Our results provide the first evidence that hCG-induced AREG contributes to aromatase expression and E2 production in the luteal phase of the menstrual cycle. A better understanding of the hormonal regulation of female reproductive function may help to develop new strategies for the treatment of clinical infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China for Young Scientists (81601253), the specific fund of clinical medical research of Chinese Medical Association (16020160632) and the Foundation from the First Affiliated Hospital of Zhengzhou University for Young Scientists to Lanlan Fang. This work was also supported by an operating grant from the National Natural Science Foundation of China (81820108016) to Ying-Pu Sun. All authors declare no conflict of interest.

PSYCHOSOCIAL STRESS AND THE MENSTRUAL CYCLE

1999 ◽  
Vol 31 (3) ◽  
pp. 393-402 ◽  
Author(s):  
KATHERINE A. SANDERS ◽  
NEVILLE W. BRUCE
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Mood States ◽  
Analysis Of Covariance ◽  
Stress Hormone ◽  
Stress Levels ◽  
The Relationship ◽  
Hormone Excretion ◽  
Phase Length

The relationship between mood states, urinary stress hormone output (adrenaline, noradrenaline and cortisol) and adequacy of the menstrual cycle was examined in 120 recorded non-conception cycles from 34 women. It was hypothesized that women with higher stress levels would be more likely to experience abnormal cycles and that within women higher stress levels would positively relate to follicular phase length and inversely relate to luteal phase length. There was a non-significant trend for women to report higher stress levels during oligomenorrhoeic and unclear cycles compared with normal cycles. Analysis of covariance indicated that there was no consistent relationship between the measures of stress used here and follicular or luteal phase length within women. There was also no consistent pattern of relationship between reported mood states and stress hormone excretion within women. Further research is warranted to understand the role of stress and subtle menstrual cycle abnormalities in female fertility.

Plasma bradykininogen and reproductive cycles: studies during the oestrous cycle and pregnancy in the rat, and in the human menstrual cycle

1976 ◽  
Vol 54 (6) ◽  
pp. 941-947 ◽  
Author(s):  
M. McDonald ◽  
A. M. Perks
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Oestrous Cycle ◽  
Menstrual Cycles ◽  
Late Luteal Phase ◽  
Human Menstrual Cycle ◽  
Reproductive Cycles ◽  
In Pregnancy

Plasma bradykininogen levels have been shown to rise about threefold late in pregnancy in the rat. However, they declined sharply 1–2 days before delivery.Plasma bradykininogen levels remained relatively unchanged through most the oestrous and menstrual cycles (rat, man). However, they showed a fall at two similar periods, in both cycles. A smaller decline occurred in metoestrus in the rat, and (probably) in the late luteal phase in the human. The largest fall took place around the time of ovulation in both the oestrous and the menstrual cycles. The decline was about 59% in the rat and 42% in the human. Bradykininogen showed no similar changes in the blood of male human controls. The suggestion that bradykinin could be involved in ovulation is discussed.

CONCENTRATION OF PROSTAGLANDIN F2α AND STEROIDS IN THE HUMAN CORPUS LUTEUM

1977 ◽  
Vol 73 (1) ◽  
pp. 115-122 ◽  
Author(s):  
I. A. SWANSTON ◽  
K. P. McNATTY ◽  
D. T. BAIRD
Keyword(s):  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Prostaglandin F2α ◽  
Corpora Lutea ◽  
Progesterone Concentration ◽  
Late Luteal Phase ◽  
Prostaglandin F ◽  
Human Corpus Luteum

SUMMARY The concentration of prostaglandin F2α (PGF2α), progesterone, pregnenolone, oestradiol-17β, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2α was significantly higher in corpora lutea immediately after ovulation (26·7 ± 3·9 (s.e.m.) ng/g, P < 0·005) and in corpora albicantia (16·3 ± 3·3 ng/g, P < 0·005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2α and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24·9 ± 6·7 μg/g) and in early luteal groups (25·7 ± 6·8 μg/g) but declined significantly (P < 0·05) to its lowest level in corpora albicantia (1·82 ± 0·66 μg/g). The concentration of oestradiol-17β in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 ± 43 ng/g, P < 0·05; weight 1·86 ± 0·18 g, P < 0·005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2α in the late luteal phase of the cycle.

scholarly journals Peak gamma frequency and cortical laminar processing are modified across the healthy menstrual cycle

2017 ◽  
Author(s):  
R.L. Sumner ◽  
R.L. McMilllan ◽  
A. D. Shaw ◽  
K.D. Singh ◽  
F. Sundram ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Gonadal Hormones ◽  
Follicular Phase ◽  
Cycle Phase ◽  
Functional Changes ◽  
Gamma Frequency ◽  
Cortical Laminar

AbstractFluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid-luteal phase when progesterone and oestradiol are highest, and early follicular phase when progesterone and oestradiol are lowest. Significantly higher (~5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modelling these changes were linked to stronger self-inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma-band oscillations.

scholarly journals Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

2019 ◽  
Vol 20 (24) ◽  
pp. 6339 ◽  
Author(s):  
Julie Gatien ◽  
Pascal Mermillod ◽  
Guillaume Tsikis ◽  
Ophélie Bernardi ◽  
Sarah Janati Idrissi ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Extracellular Vesicles ◽  
Luteal Phase ◽  
Early Embryo ◽  
Proton Nuclear Magnetic Resonance ◽  
Resonance Spectroscopy ◽  
Metabolomic Profiling ◽  
Late Luteal Phase

Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs’ metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development.

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