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The distribution of progestin receptor mRNA in rat brainstem

https://doi.org/10.1016/S1567-133X(02)00011-XGet rights and content

Abstract

Hypothalamic sites wherein P4, through progestin receptor, (Pgr; commonly abbreviated PR), maximizes the expression of female sexual behaviors and gonadotropin surge release have been studied intensively. However, little is known regarding PR expression in brainstem regions likely to regulate changes in autonomic functions observed when P4 levels are elevated (i.e. pregnancy). Using in situ hybridization, we found PR mRNA-containing cells widely distributed throughout the brainstem of ovariectomized, estradiol-treated Sprague–Dawley rats, with high expression in regions including the medial vestibular nucleus, nucleus of the solitary tract, substantia nigra (compact part), ventral tegmental area, hypoglossal nucleus, locus coeruleus, Purkinje cell layer of the cerebellum and inferior olivary complex. We also detected moderate to high levels of PR gene expression in several regions, such as the trapezoid nucleus, facial nucleus, periaqueductal gray regions, and rostral ventrolateral medulla. These results demonstrate that PR expression is widespread in the brainstem and identify nuclei wherein P4 may act to influence a number of physiological functions during pregnancy.

Introduction

The ovarian steroid hormone progesterone (P4) is a well-known regulator of female reproductive physiology [9]. As a result of intensive research efforts, the hypothalamic and midbrain sites wherein P4 exerts its effects on ovulation [2], [5] and mating behavior [12], [13] have been well characterized. In contrast, little attention has been directed toward identifying the brainstem neurons through which P4 modulates respiratory, cardiovascular and nociceptive functions during periods when P4 levels are elevated. To address this issue, we performed an extensive mapping of the distribution of PR mRNA in female rat brainstem using a well-characterized ovariectomized, estradiol-treated animal model. This model has been shown to maximize PR expression, presumably through induction of the gene by estradiol [7]. We also included sections from the anteroventral periventricular (AVPV) nucleus of the preoptic area as positive controls, because PR gene expression is known to be high in this region [25].

Section snippets

Materials and methods

Animals used in these studies were maintained in accordance with the NIH Guide for the Care and Use of Laboratory Animals and protocols were approved by the Institutional Animal Care and Use Committee of the University of Massachusetts. Adult female Sprague–Dawley rats (225–250 g; Zivic Miller, Potersville, PA) were bilaterally ovariectomized and treated with two Silastic capsules of E2 (200 μg/ml in sesame oil) as described previously [22]. Two days after E2 treatment, animals were euthanized

Results

Relative levels of PR gene expression in sensory nuclei are shown in Table 1. Several auditory nuclei (Fig. 1E) expressed PR mRNA with high levels found in the lateroventral periolivary nucleus and moderate levels in the trapezoid nucleus, medioventral periolivary nucleus and medial superior olive. The ventral cochlear and the dorsal cochlear nuclei contained low levels of PR gene expression. No signal was detected in the nucleus of the lateral lemniscus, superior colliculus, inferior

Discussion

The results of the present study provide new information regarding PR gene expression in the brainstem of the female rat. Most notably, we detected PR mRNA in regions that regulate respiration, nociception, vestibular function, motor performance and blood pressure, functions that undergo important adaptations during the luteal phase and pregnancy when P4 levels are elevated [1], [11], [23], [27].

Activation of PR in the brainstem may be important for inducing changes in the regulation of

Acknowledgements

Supported by National Institutes of Mental Health; grant number MH12347-02 to MAC and National Institutes of Child Health and Development; grant number HD27305 to SLP. The authors wish to thank Drs. R. Thomas Zoeller and Cliff D. Carpenter for their critical reviews of early drafts of this manuscript.

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