Our study has attempted to clarify the developmental profile of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) along with the expression of their receptors in the rat hypothalamus. Radioimmunoassay (RIA) of dissected hypothalamic tissue revealed that ANP rose from 167 +/- 50 pg/mg protein immediately after birth to 516 +/- 78 pg/mg protein in the next 24 h and to 928 +/- 100 pg/mg protein by postnatal day (PD) 5. A second increment of ANP in the hypothalamus was noted between PD 10 and PD 20 (from 780 +/- 110 to 2,650 +/- 136 pg/mg protein). These changes were not gender-related and consistent with a rise of ANP mRNA. Diethylstilbestrol treatment of immature rats increased hypothalamic ANP concentration from 2.11 +/- 0.24 to 2.97 +/- 0.44 ng/mg protein (P<0.001), but equine chorionic gonadotropin had no effect, indicating that estrogen is a potential stimulus of ANP only at supra-physiological concentrations. CNP, the most abundant natriuretic peptide in the brain, gradually increased in the developing hypothalamus, but did not plateau at PD 20. Reverse transcription-polymerase chain reaction analysis of ANP receptor mRNA demonstrated higher guanylyl cyclase (GC) A, no changes in GC-B, and lower C-receptor levels in adult compared to newborn rats. In conclusion, we have shown that hypothalamic ANP undergoes a dramatic rise after birth, and progresses further until the 3rd postnatal week. ANP and CNP changes in the developing hypothalamus can influence brain maturation.