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Early postnatal stimulation alters pregnane neurosteroids in the hippocampus

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Abstract

Rationale

The progesterone metabolite 5α-pregnane-3α-ol-20-one (3α,5α-THP) is an important modulator of the hypothalamic–pituitary–adrenal axis and stress-induced corticosterone response. Typically, 3α,5α-THP levels are increased in response to acute stress, which may then reduce corticosterone release from the adrenals. Early postnatal stimulation is a developmental stressor that can produce pervasive endocrine effects.

Objectives

The present studies investigated the effects of early postnatal stimulation on plasma progestin and corticosterone levels and hippocampal progestin levels of rats.

Methods

On postnatal days 9 and 10, rats were either left in their home cage undisturbed or injected intraperitoneally as a means of early stimulation (ES). Tissues were collected on either postnatal day 10 (6 h after last handling experience) or adulthood. Plasma corticosterone, progesterone, and 3α,5α-THP and hippocampal progesterone and 3α,5α-THP were measured by radioimmunoassay.

Results

On postnatal day 10, plasma, but not hippocampal, levels of progesterone and 3α,5α-THP were significantly lower among rats exposed to ES than control rats. These effects occurred concomitant with a tendency for plasma corticosterone to be higher among ES compared to control rats. In adulthood, hippocampal 3α,5α-THP was significantly lower among ES vs control rats.

Conclusions

Together, these data suggest that ES may influence immediate secretion of 3α,5α-THP and corticosterone and have pervasive effects in adulthood on the biosynthesis and/or metabolism of progestins in the hippocampus.

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Acknowledgements

This research was supported by grants to CAF from the National Institute of Mental Health (MH06769), and to ARB-K from the National Institute of Neurological Disorders and Stroke (NS38595).

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Authors and Affiliations

  1. Department of Psychology, University at Albany, Albany, NY,, USA

    Cheryl A. Frye

  2. Biological Sciences, University at Albany, Albany, NY,, USA

    Cheryl A. Frye

  3. Center for Neuroscience Research, University at Albany, Albany, NY,, USA

    Cheryl A. Frye

  4. Life Sciences Research, University at Albany, Life Sciences Research Building-1058, 1400 Washington Avenue, Albany, NY, 12222, USA

    Cheryl A. Frye & Madeline E. Rhodes

  5. Division of Neurology, The Children’s Hospital of Philadelphia, PA, USA

    YogendraSinh H. Raol & Amy R. Brooks-Kayal

  6. Departments of Neurology and Pediatrics, The University of Pennsylvania, PA, USA

    Amy R. Brooks-Kayal

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  1. Cheryl A. Frye
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  2. Madeline E. Rhodes
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  4. Amy R. Brooks-Kayal
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Correspondence to Cheryl A. Frye.

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Frye, C.A., Rhodes, M.E., Raol, Y.H. et al. Early postnatal stimulation alters pregnane neurosteroids in the hippocampus. Psychopharmacology 186, 343–350 (2006). https://doi.org/10.1007/s00213-005-0253-7

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  • DOI: https://doi.org/10.1007/s00213-005-0253-7

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