Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle

Palumbo, Marco; Salvestroni, C.; Gallo, R.; Guo, Aili; Genazzani, Alessandro; Artini, P. G.; Petraglia, Felice; Genazzani, Ar

doi:10.1007/bf03349832

Cited by 71 publications

(51 citation statements)

References 14 publications

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“…Steroids, such as 17β-estradiol and THP, remain relatively low in the early phases of puberty but increase throughout development, with peak levels of THP noted during stages IVand V (Fadalti et al, 1999) prior to the onset of fluctuations induced by the menstrual cycle (see below). High circulating and CNS levels of THP have been noted in the mouse and rat immediately before puberty onset (Mannan & O'Shaughnessy, 1988;Palumbo et al, 1995), followed by a decline (Palumbo et al, 1995;Shen et al, 2007).…”

Section: Pubertymentioning

confidence: 99%

“…Although an array of hormonally mediated events occur at this time, the onset of puberty is associated with a decline in circulating levels of THP (Palumbo et al, 1995;Fadalti et al, 1999). The onset of puberty also increases the likelihood of developing anxiety disorders, including panic disorder, twice as likely in girls compared to boys (Hayward & Sanborn, 2002).…”

Section: Pubertymentioning

confidence: 99%

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Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Smith

Shen

Gong

et al. 2007

Pharmacology & Therapeutics

214

197

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Neurosteroids, such as the progesterone metabolite 3α-OH-5α[β]-pregnan-20-one (THP or [allo] pregnanolone), function as potent positive modulators of the GABA A receptor (GABAR) when acutely administered. However, fluctuations in the circulating levels of this steroid at puberty, across endogenous ovarian cycles, during pregnancy or following chronic stress produce periods of prolonged exposure and withdrawal, where changes in GABAR subunit composition may occur as compensatory responses to sustained levels of inhibition. A number of laboratories have demonstrated that both chronic administration of THP as well as its withdrawal transiently increase expression of the α4 subunit of the GABAR in several areas of the central nervous system (CNS) as well as in in vitro neuronal systems. Receptors containing this subunit are insensitive to benzodiazepine (BDZ) modulation and display faster deactivation kinetics, which studies suggest underlie hyperexcitability states. Similar increases in α4 expression are triggered by withdrawal from other GABA-modulatory compounds, such as ethanol and BDZ, suggesting a common mechanism. Other studies have reported puberty or estrous cycle-associated increases in δ-GABAR, the most sensitive target of these steroids which underlies a tonic inhibitory current. In the studies reported here, the effect of steroids on inhibition, which influence anxiety state and seizure susceptibility, depend not only on the subunit composition of the receptor but also on the direction of Cl -current generated by these target receptors. The effect of neurosteroids on GABAR function thus results in behavioral outcomes relevant for pubertal mood swings, premenstrual dysphoric disorder and catamenial epilepsy, which are due to fluctuations in endogenous steroids.

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Section: Pubertymentioning

confidence: 99%

Section: Pubertymentioning

confidence: 99%

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Smith

Shen

Gong

et al. 2007

Pharmacology & Therapeutics

214

197

View full text Add to dashboard Cite

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“…Rat hypothalamic and hippocampal contents of allopregnanolone show significant changes during the estrous cycle (7,8). No data on brain allopregnanolone content are available in aged rats.…”

Section: Introductionmentioning

confidence: 99%

Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats

Bernardi

Salvestroni

Casarosa³

et al. 1998

European Journal of Endocrinology

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Objective: Allopregnanolone is a potent neuroactive steroid hormone produced in the brain and in peripheral endocrine glands. The present study investigated possible age-related variations in allopregnanolone content in brain areas, endocrine glands and serum of male rats. Design: Wistar male rats were categorized into 5 groups (6 rats in each) according to age: 6, 12, 16, 18 and 20 months respectively. Methods: Allopregnanolone content in acidic homogenates of brain cortex, hypothalamus, pituitary, adrenals and gonads was measured by a specific radioimmunoassay. Serum allopregnanolone, corticosterone and testosterone were also assayed by radioimmunoassay. Results: Brain cortex allopregnanolone content decreased significantly with age, while hypothalamic allopregnanolone content remained constant until 18 months and increased significantly at 20 months. Pituitary content showed a significant age-related reduction. Adrenal allopregnanolone content remained constant until 18 months, and was significantly higher at 20 months. Testis and serum allopregnanolone contents showed significant age-related increases. Serum testosterone levels showed an age-related decrease, while no age-related variation in serum corticosterone was found. Conclusions:The present study showed a significant impact of aging on allopregnanolone contents in brain, endocrine glands and serum, showing an age-related decrease in brain cortex and pituitary, and an age-related increase in testes, adrenals and serum.

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“…1) is upregulated on demand (Reddy and Rogawski 2002). Altered brain levels of 3␣,5␣-reduced neurosteroids have been demonstrated during stress (Purdy et al 1991) and depression (Uzunova et al 1998), over the estrus cycle (Palumbo et al 1995), and after ethanol ingestion ( VanDoren et al 2000); however, the mediating physiological determinant in the rise and fall of neurosteroid levels under these different conditions remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Neurosteroids Involved in Regulating Inhibition in the Inferior Colliculus

Saalmann

Morgan²,

Calford³

2006

Journal of Neurophysiology

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. Fast inhibitory neurotransmission in the brain is largely mediated by the ␥-aminobutyric acid-type A (GABA A ) receptor. The 3␣,5␣-reduced neurosteroids (e.g., allopregnanolone) are the most potent endogenous modulators of the GABA A receptor. Although it is known that 3␣,5␣-reduced neurosteroid levels change during stress or depression and over the estrus cycle, a basic physiological role consistent with their pharmacological action remains elusive. We used the unique architecture of the auditory midbrain to reveal a role for 3␣,5␣-reduced neurosteroids in regulating inhibitory efficacy. After blocking the massive GABAergic projection from the dorsal nucleus of the lateral lemniscus (DNLL) to the contralateral central nucleus of the inferior colliculus (ICC) in anesthetized rats, a reactive increase in the efficacy of other inhibitory circuits in the ICC (separable because of the dominant ear that drives each circuit) was demonstrated with physiological measures-singleneuron activity and a neural-population-evoked response. This effect was prevented by blocking 3␣,5␣-reduced neurosteroid synthesis with a 5␣-reductase inhibitor: finasteride. Immunohistochemistry confirmed that the DNLL blockade induced an increase in 3␣,5␣-reduced neurosteroids in the contralateral ICC. This study shows that when GABAergic inhibition is reduced, the brain compensates within minutes by locally increasing synthesis of neurosteroids, thereby balancing excitatory and inhibitory inputs in complex neural circuits.

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Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle

Cited by 71 publications

References 14 publications

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats

Neurosteroids Involved in Regulating Inhibition in the Inferior Colliculus

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