Prenatal D-Amphetamine exposure alters the hypothalamus pituitary axis response that regulates PRL secretion in adulthood. Involvement of stress and sexual steroids

SANTONJA FLORENCIA ELEONORA; PIETROBON ELISA OLIVIA; NEIRA FLAVIA JUDITH; SÁNCHEZ MARÍA BELÉN; MORENO SOSA MARÍA TAMARA; JAHN GRACIELA ALMA; BREGONZIO CLAUDIA; VALDEZ SUSANA RUTH; SOAJE MARTA

Congreso; IV Reunión conjunta de Sociedades de Biología dela República Argentina; 2020

Prenatal amphetamine exposure (PEA) induces long-lasting changes that are evident even in adulthood. D-amphetamine is a stimulant of CNS andacts on the dopaminergic and noradrenergic systems. Prolactin (PRL) synthesis and secretion is regulated by an inhibitory hypothalamic tone exertedby tuberoinfundibular dopaminergic neurons (TIDA). Dopamine (DA) is synthesized by tyrosine hydroxylase (TH) and released into portal blood toact on pituitary dopaminergic receptors (D2R) to inhibit PRL. Stress and sex steroids modulate PRL release, and PRL regulates its own secretionthrough a negative feedback that acts on hypothalamus and pituitary gland. Our aim was to evaluate the effect of PEA on PRL secretion in adult maleand female ovariectomized/ovariectomized plus estradiol (OVX/OVX + E2) Wistar rats under basal and stress conditions and its interaction with thedopaminergic system. Female rats were treated daily with D-amphetamine 2.5 mg/kg i.p./saline (SAL) during days 15 to 21 of pregnancy. Theirfemale offspring were OVX at day 60 under anesthesia (ketamine/xylazine) and treated 15 days later with estrogen/oil (E2; 2 × 5 μg/rat/24 h). Maleand (OVX/OVX + E2) female offspring, were exposed to immobilization stress for 30 min. After sacrifice, blood and tissue samples were collectedfor PRL measurement by RIA, and pituitary PRL content, D2R and prolactin receptor long isoform (PRLRL) by real time PCR and Western blot(WB). Phospho- tyrosine hydroxylase (p-TH-Ser 40) expression was determined by WB in medial basal hypothalamus (MBH) extracts. ComparativeCT method was used, and RNA expression was normalized with respect to S16 gen (mean ± SEM; N = 6–8). Data were analyzed using two-wayANOVA and Student’s t-test. Serum PRL levels increased significantly in response to stress in male and OVX + E2 vs. control (SAL) rats, and PEAprevented this rise. E2 increased pituitary PRL expression (PCR) in basal and stressed conditions, and PEA reduced PRL content (WB) in OVX andOVX + E2 rats. Basal male D2R expression was lower than in females, and E2 treatment of OVX rats reduced D2R expression in PEA groups interms of RNA and protein both in basal conditions and in response to stress. PEA and stress did not modify male PRLRL. However, stress reducedPRLRL expression in OVX and OVX + E2, and this effect was prevented by PEA. Moreover, stress reduced MBH p-TH in PEA OVX + E2 rats. Inconclusion, prenatal amphetamine exposure may deregulate hypothalamus-pituitary axis, affecting PRL synthesis and secretion. E2 treatment maysensitize this effect.