Progesterone increases brain‐derived neuroptrophic factor expression and protects against glutamate toxicity in a mitogen‐activated protein kinase‐ and phosphoinositide‐3 kinase‐dependent manner in cerebral cortical explants

Kaur, Paramjit; Jodhka, Parmeet K.; Underwood, Wendy; Bowles, Courtney; Fiebre, Nancy Ellen C. de; Fiebre, Christopher M. de; Singh, Meharvan

doi:10.1002/jnr.21370

Cited by 144 publications

(140 citation statements)

References 54 publications

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“…These findings are consistent with the wealth of data showing that progesterone is an important respiratory stimulant in adults (Bayliss et al, 1987;Hannhart et al, 1990;Joseph et al, 2002), and the data showing that in newborn rats, progesterone affects the hypoxic ventilatory response without affecting baseline ventilation (Lefter et al, 2007(Lefter et al, , 2008. Because progesterone promotes the expression of neural growth factors (Gibbs, 1999;Kaur et al, 2007) that are involved in the postnatal development of peripheral chemoreceptors (Brady et al, 1999;Wang and Bisgard, 2005), we also tested the hypothesis that mifepristone treatment impairs carotid body growth. However, carotid body and glomic tissue size were not affected in mifepristone-treated pups, and these findings do not support that hypothesis.…”

Section: Discussionsupporting

confidence: 79%

Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups

2012

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We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between postnatal days 3 and 15. In 11-14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity-nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats. Keywordscarotid sinus nerve; whole-body plethysmography; hypoxia; nicotine receptor agonist; progesterone receptor antagonist; newborn Progesterone is a respiratory stimulant that acts both on the central nervous system (CNS) and on peripheral chemoreceptors to enhance resting minute ventilation (Bayliss et al., 1987), the hypoxic ventilatory response (Joseph et al., 2002), and the carotid sinus nerve response to hypoxia (Hannhart et al., 1990). These effects of progesterone are well described in adults and also occur in newborn rats in which chronic progesterone exposure enhances the hypoxic ventilatory response and reduces apnea frequency under normoxia or hypoxia (Lefter et al., 2007(Lefter et al., , 2008. This has potential far-reaching implications because progesterone-based hormone replacement therapy reduces the occurrence of sleep apneas in

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Section: Discussionsupporting

confidence: 79%

Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups

2012

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“…Further its effects in direct modulation of neurotransmitter receptor functions, and antioxidant activities have been attributed for decrease in latency of ABR in estrogenic phase [27]. However, presently there are emerging findings suggesting that progesterone is neuroprotective by increasing brain derived neurotrophic factor expression and by protecting against glutamate toxicity in a mitogen activated protein kinase and phosphoinositide-3 kinase dependent manner in cerebral cortical explants [28]. Evidence also shows that in females with premature ovarian failure estrogen replacement alone increase the peak latency of wave V and IPL I-V while combination of estrogen and progesterone decreases the latencies [29].…”

Section: Discussionmentioning

confidence: 99%

Pre- and Postovulatory Auditory Brainstem Response in Normal Women

Upadhayay

Paudel

Singh

et al. 2011

Indian J Otolaryngol Head Neck Surg

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Studies with ovarian hormones on auditory brainstem response (ABR) have conflicting reports although women have ABR shorter than men. This study compared ABR between pre-and postovulatory phases of menstrual cycle in consenting 40 healthy female volunteers (age 19 ± 2.35 years). The study was conducted under standard laboratory conditions (room temperature 26 ± 2°C) using Neuropack (Nihon Kohden machine, NM-420S; H636, Japan) and earphone dynamic receiver ELEGA (Type DR-531; no.237, Japan) in sound proof room. Ears were stimulated simultaneously using standard protocol. ABR was recorded in pre-and postovulatory phases. Ovulation was estimated by measuring basal body temperature. The ABR wave latencies (WLs) I, II, III, IV, V and inter-peak latencies (IPLs) I-III, III-V, I-V were compared between the two phases of menstrual cycle using paired t test. The postovulatory phase had shorter WL V (5.71 ± 0.18 ms vs. 5.81 ± 0.19 ms, p \ 0.01), IPL III-V (1.89 ± 0.16 ms vs. 1.94 ± 0.19 ms, p \ 0.05), and I-V (3.88 ± 0.16 ms vs. 3.95 ± 0.18 ms, p \ 0.05) than in preovulatory. Other WLs and IPLs showed decreasing trend in postovulatory phase. ABR is better in postovulatory phase as compared to preovulatory phase probably due to progesterone hormone which might be involved in modulating auditory hearing pathway at postovulatory phase.

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“…In fact, estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat (69). Steroids such as progesterone and estrogen have been shown to have neuroprotective and antiapoptotic effects in a number of cell types (37,58,67). Regulation of steroid production by cholangiocytes may be a key mechanism in controlling cholangiocyte growth and responses to injury and deserves further evaluation.…”

Section: Discussionmentioning

confidence: 99%

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Glaser¹,

DeMorrow²,

Francis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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During cholestatic liver diseases, cholangiocytes express neuroendocrine phenotypes and respond to a number of hormones and neuropeptides by paracrine and autocrine mechanisms. We examined whether the neuroendocrine hormone progesterone is produced by and targeted to cholangiocytes, thereby regulating biliary proliferation during cholestasis. Nuclear (PR-A and PR-B) and membrane (PRGMC1, PRGMC2, and mPRα) progesterone receptor expression was evaluated in liver sections and cholangiocytes from normal and bile duct ligation (BDL) rats, and NRC cells (normal rat cholangiocyte line). In vivo, normal rats were chronically treated with progesterone for 1 wk, or immediately after BDL, rats were treated with a neutralizing progesterone antibody for 1 wk. Cholangiocyte growth was measured by evaluating the number of bile ducts in liver sections. The expression of the progesterone synthesis pathway was evaluated in liver sections, cholangiocytes and NRC. Progesterone secretion was evaluated in supernatants from normal and BDL cholangiocytes and NRC. In vitro, NRC were stimulated with progesterone and cholangiocyte supernatants in the presence or absence of antiprogesterone antibody. Aminoglutethimide was used to block progesterone synthesis. Cholangiocytes and NRC express the PR-B nuclear receptor and PRGMC1, PRGMC2, and mPRα. In vivo, progesterone increased the number of bile ducts of normal rats, whereas antiprogesterone antibody inhibited cholangiocyte growth stimulated by BDL. Normal and BDL cholangiocytes expressed the biosynthetic pathway for and secrete progesterone. In vitro, 1) progesterone increased NRC proliferation; 2) cholangiocyte supernatants increased NRC proliferation, which was partially inhibited by preincubation with antiprogesterone; and 3) inhibition of progesterone steroidogenesis prevented NRC proliferation. In conclusion, progesterone may be an important autocrine/paracrine regulator of cholangiocyte proliferation.

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Progesterone increases brain‐derived neuroptrophic factor expression and protects against glutamate toxicity in a mitogen‐activated protein kinase‐ and phosphoinositide‐3 kinase‐dependent manner in cerebral cortical explants

Cited by 144 publications

References 54 publications

Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups

Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups

Pre- and Postovulatory Auditory Brainstem Response in Normal Women

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

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