ESTROGEN AND PROGESTERONE-RECEPTOR EXPRESSION IN NEUROENDOCRINE AND RELATED NEURONS OF THE PUBERTAL FEMALE MONKEY HYPOTHALAMUS

Expression of hypothalamic estrogen receptors (ER) and progesterone re ceptors (PR) is bars ly evident in prepubertal monkeys but is prominen t in adults. To investigate whether adult patterns of ER and PR expres sion are established in mid-pubertal female cynomolgus monkeys, we lab eled neuroendocrine (NEU) neurons by microinjection of retrograde trac er into the median eminence, and then identified ER and PR by specific immunostaining in separate sets of hypothalamic sections. ER and PR a ppeared in the cytoplasm and nuclei of cells identified exclusively as neurons, and retrograde tracer remained clearly visible in the cytopl asm of NEU neurons after immunostaining. Numbers of NEU and related ne urons expressing ER or PR were quantified in principal hypothalamic re gions. In the supraoptic nucleus, almost all neurons analyzed (n = 580 ) contained ER (94%) with many also NEU (73% ER + NEU), while lesser a mounts of the neurons examined (n = 214) expressed PR (75%) and were N EU (53% PR + NEU). In the paraventricular nucleus, most of the neurons analyzed (n = 302) contained ER (90% ER; 54% ER + NEU), but few of th e neurons studied (n = 269) contained PR (34% PR; 19% PR + NEU). In th e periventricular zone, nearly all neurons examined (n = 795) containe d ER (95% ER; 48% ER + NEU), but fewer of those studied (n = 298) exhi bited PR (79% PR; 47% PR + NEU). In the arcuate-periventricular zone, all neurons examined (n = 542) contained ER (100%) but few were NEU (4 % ER + NEU), while nearly all neurons studied (n = 418) contained PR ( 95%), some of which were NEU (21% PR + NEU). Neurons expressing ER wer e also prevalent in areas without NEU labeling, including the diagonal band of Broca, medial preoptic area, and mammillary bodies, but were less common in the septum and dorsomedial hypothalamus. Likewise, neur onal PR expression was seen frequently in the mammillary bodies, but o ccurred less often in the diagonal band of Broca, medial preoptic area , and dorsomedial hypothalamus. Neurons in the suprachiasmatic nucleus and lateral hypothalamic area lacked retrograde labeling. These resul ts identify the principal sites and subsets of NEU and related neurons which express ER and PR in the mid-pubertal female monkey hypothalamu s. They appear to correlate well with known populations of steroid-sen sitive NEU neurons present in these areas in adults. The data also sug gest that functional patterns of ER and PR expression arise upon react ivation of the hypothalamic-pituitary-gonadal axis at puberty. The deg rees of receptor expression and of nuclear translocation most likely r eflect peripubertal changes in the levels of gonadal steroids. Taken t ogether, these results provide important insights into the mechanisms and development of neuroendocrine control during the pubertal period i n primates.