scholarly journals Short-Term Pharmacological Suppression of the Hyperprolactinemia of Infertile hCG-Overproducing Female Mice Persistently Restores Their Fertility

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 5980-5992 ◽  
Author(s):  
Laura D. Ratner ◽  
Betina Gonzalez ◽  
Petteri Ahtiainen ◽  
Noelia P. Di Giorgio ◽  
Matti Poutanen ◽  
...  
Keyword(s):  
Early Stage ◽  
Reproductive Function ◽  
Term Treatment ◽  
Endocrine Disorders ◽  
Short Term ◽  
Short Term Treatment ◽  
Adult Age ◽  
Female Mice ◽  
Adult Mice ◽  
Hypothalamic Pituitary Axis

Abstract Female infertility is often associated with deregulation of hormonal networks, and hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis affecting the reproductive functions. We have shown previously that transgenic female mice overexpressing human chorionic gonadotropin β-subunit (hCGβ+ mice), and producing elevated levels of bioactive LH/hCG, exhibit increased production of testosterone and progesterone, are overweight and infertile, and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adult age. In the present study, we analyzed the influence of the hyperprolactinemia of hCGβ+ females on their reproductive phenotype by treating them with the dopamine agonists, bromocriptine and cabergoline. Long-term bromocriptine treatment of adult mice was effective in the control of obesity, pituitary growth, and disturbances in the hormone profile, demonstrating that hyperprolactinemia was the main cause of the hCGβ+ female phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on 5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal function, and recovered fertility of adult hCGβ+ females after hormone-induced and natural ovulation. The same cabergoline treatment in the short term applied on 3-month-old hCGβ+ females failed to recover their reproductive function. Hence, we demonstrated that the short-term cabergoline treatment applied at a critical early stage of the phenotype progression effectively prevented the hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing females.

scholarly journals Short-term enhancement of motor neuron synaptic exocytosis during early aging extends lifespan in Caenorhabditis elegans

2020 ◽  
Vol 245 (17) ◽  
pp. 1552-1559
Author(s):  
Tsui-Ting Ching ◽  
Yen-Chieh Chen ◽  
Guang Li ◽  
Jianfeng Liu ◽  
X Z Shawn Xu ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Early Stage ◽  
Functional Decline ◽  
The Elderly ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
C Elegans ◽  
Synaptic Exocytosis

Age-related mobility decline is often associated with negative physical and psychological outcomes, such as frailty, in the elderly population. In C. elegans, during the early stage of the aging process, a progressive deficit of synaptic exocytosis in the motor neurons results in a functional decline at the neuromuscular junctions, which eventually leads to degeneration of both neurons and muscles. This age-dependent functional decline can be ameliorated by pharmacological interventions, such as arecoline, a muscarinic AChR agonist known to promote synaptic exocytosis at the neuromuscular junctions. In this study, we found that a short-term treatment of arecoline during the early stage of aging, when the NMJ functional decline begins, not only slows muscle tissue aging, but also extends lifespan in C. elegans. We have also demonstrated that arecoline acts on the GAR-2/PLCβ pathway in the motor neurons to increases longevity. Together, our findings suggest that synaptic transmission in aging motor neurons may serve as a potential target for pharmacological interventions to promote both health span and lifespan, when applied at the early stage aging. Impact statement The functional decline of motor activity is a common feature in almost all aging animals that leads to frailty, loss of independence, injury, and even death in the elderly population. Thus, understanding the molecular mechanism that drives the initial stage of this functional decline and developing strategies to increase human healthspan and even lifespan by targeting this process would be of great interests to the field. In this study, we found that by precisely targeting the motor neurons to potentiate its synaptic releases either genetically or pharmacologically, we can not only delay the functional aging at NMJs but also slow the rate of aging at the organismal level. Most importantly, we have demonstrated that a critical window of time, that is the early stage of NMJs functional decline, is required for the beneficial effects. A short-term treatment within this time period is sufficient to extend the animals’ lifespan.

EFFECT OF PROGESTERONE AND OESTROGEN ON PREGNANCY AND EMBRYONIC MORTALITY IN ADULT MICE FOLLOWING SUPEROVULATION TREATMENT

1960 ◽  
Vol 20 (1) ◽  
pp. 1-8 ◽  
Author(s):  
RUTH E. FOWLER ◽  
R. G. EDWARDS
Keyword(s):  
Early Pregnancy ◽  
Term Treatment ◽  
Vaginal Smears ◽  
Short Term ◽  
Short Term Treatment ◽  
Adult Mice ◽  
Foetal Mortality ◽  
Exogenous Oestrogen ◽  
Oestradiol Benzoate ◽  
Endogenous Oestrogen

SUMMARY The effects of exogenous oestrogen and progesterone on implantation and foetal mortality were studied in mice following induced superovulation with gonadotrophins. Short-term treatment with progesterone during early pregnancy did not influence implantation or foetal mortality, but 2 mg daily from days 2 to 12 reduced the number of embryos that implanted and increased foetal mortality after implantation. These effects of progesterone were more severe when few embryos were implanted. Oestradiol benzoate (OB), given after mating, reduced fertility by decreasing the proportion of mice with implanted embryos, causing cornification of the vagina in many mice during pregnancy. Administration of progesterone with OB did not alleviate these effects. Administration of OB before superovulation, or lengthening the interval between the injections of PMS and HCG in order to extend the period of uterine stimulation by endogenous oestrogen, interfered with ovulation in some mice. Approx. one-quarter of the mice given oestrogen had cornified vaginal smears during early pregnancy. Both treatments decreased the numbers of mice with implanted embryos.

scholarly journals KIDNEY INJURY MOLECULE-1 AS AN EARLY AMIKACIN-INDUCED NEPHROTOXICITY MARKER IN PATIENTS WITH SEPSIS HOSPITALIZED IN THE INTENSIVE CARE UNIT

2019 ◽  
pp. 277-279
Author(s):  
TRISNI UNTARI DEWI ◽  
INSTIATY . ◽  
RUDIANTO SEDONO ◽  
GESTINA ALISKA ◽  
MUHAMMAD KHIFZHON AZWAR ◽  
...  
Keyword(s):  
Intensive Care ◽  
Kidney Injury ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Safe Level ◽  
Study Results ◽  
Early Biomarker ◽  
Kidney Injury Molecule 1 ◽  
Trough Plasma

Objective: This study sought to determine the correlation between trough plasma amikacin concentrations and urinary normalized kidney injurymolecule-1 (KIM-1) concentrations as an early biomarker of nephrotoxicity in patients with sepsis who are hospitalized in an intensive care unit.Methods: In this pilot study, 12 patients with sepsis were treated with amikacin 1000 mg/day between May 2015 and September 2015. The correlationbetween trough plasma amikacin concentrations measured after the third dose and the elevation of urinary normalized KIM-1 concentrations afterthe third amikacin dose relative to the first/second dose was evaluated.Results: In total, three patients had trough plasma amikacin concentrations exceeding the safe level (>10 μg/ml). Furthermore, eight patientsdisplayed higher normalized KIM-1 concentrations after third dose than after the first/second dose; however, there was no correlation betweentrough amikacin concentrations and the elevation of urinary normalized KIM-1 concentrations (r=0.3, p=0.3).Conclusion: The study results illustrated that short-term treatment with an amikacin dose of 1000 mg/day was generally safe in patients with sepsis.

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