To better understand the role of progestins in the C1 area of the rostral ventrolateral medulla (RVLM), immunocytochemical localization of progestin receptors (PRs) was combined with tyrosine hydroxylase (TH) in single sections of RVLM from proestrus rat brains prepared for light and electron microscopy. By light microscopy, PR-immunoreactivity (-ir) was detected in a few nuclei that were interspersed between TH-labeled perikarya and dendrites. Electron microscopy revealed that PR-ir was in several extranuclear locations. The majority of PR-labeling was in non-TH immunoreactive axons (51 ± 9%) near the plasma membrane. Additional dual labeling studies revealed that PRimmunoreactive axons could give rise to terminals containing the GABAergic marker GAD65. PRir also was found in non-neuronal processes (29 ± 9%), some resembling astrocytes. Occasionally, PR-ir was in non-TH-labeled terminals (10 ± 3%) affiliated with clusters of small synaptic vesicles, or in patches contained in the cytoplasm of dendrites (10 ± 1%). These findings suggest that progestins can primarily modulate neurons in the C1 area of the RVLM by presynaptic mechanisms involving GABAergic transmission. Moreover, they suggest that PR activation may contribute to progestin's effects on arterial blood pressure during pregnancy as well as to sex differences in central cardiovascular regulation.
KeywordsBaroreceptor; Electron microscopy; Bulbospinal neurons; Presynaptic profiles; GABA; Glia Ovarian hormones, especially estrogens and progestins, regulate arterial blood pressure (ABP) and cardiovascular tone. Within the CNS, estrogens are known to act within the wellestablished medullary sites that regulate sympathetic outflow (for review see [32]). In particular, local injections of 17β-estradiol into the rostroventrolateral medulla (RVLM), which contains sympathoexcitatory bulbospinal neurons and is critical for tonic (resting) and reflex control of systemic arterial pressure [1,7], decreases sympathetic tone [30,31]. Our recent study revealed that estrogens modulate calcium currents in C1 catecholaminergic bulbospinal neurons in the RVLM and that estrogen receptor (ER) alpha and beta have unique distributions relative to C1 neurons [39].☆ Grant support: NIH grants HL18974, DA08259 (TAM), NS07080 and T32 DK07313 (E.M.W.).