PRENATAL D-AMPHETAMINE EXPOSURE ALTERS THE HYPOTHALAMUS PITUITARY AXIS RESPONSE THAT REGULATES PRL SECRETION IN ADULTHOOD. INVOLVEMENT OF STRESS AND SEXUAL STEROIDS

PIETROBON ELISA O; JAHN GRACIELA A; SOAJE MARTA; SANTONJA FLORENCIA ELEONOTA; MORENO SOSA MARÍA TAMARA; VALDEZ SUSANA R; SÁNCHEZ MARÍA BELÉN; BREGONZIO CLAUDIA

Buenos Aires

Congreso; IV Reunión Conjunta de Sociedades de Biología de la República Argentina; 2020

Sociedad Argentina de Biología

Prenatal amphetamine exposure (PEA) induces long-lasting changes that are present even in adulthood. D-amphetamine is a stimulant of CNS and acts on the dopaminergic and noradrenergic systems. Prolactin (PRL) synthesis and secretion is regulated by an inhibitory hypothalamic tone exerted by tuberoinfundibular dopaminergic neurons (TIDA). Dopamine (DA) is synthesized by tyrosine hydroxylase (TH) and released into portal blood to act on pituitary dopaminergic receptors (D2R) to inhibit PRL. Stress and sex steroids modulate PRL release, and PRL regulates its own secretion through a negative feedback that acts on hypothalamus and pituitary gland. Our aim was to evaluate the effect of PEA on PRL secretion in adult male and female (Ovariectomized (OVX) /OVX+E2) Wistar rats under basal and stress conditions and its interaction with the dopaminergic system. Female rats were treated daily with D-amphetamine 2.5mg/kg i.p/saline (SAL) during days 15 to 21 of pregnancy. Their female offspring were OVX at day 60 and treated 15 days later with estrogen/oil (E2; 2 x 5ug/rat/24 h). Male and female offspring were exposed to immobilization stress during 30 min. After sacrifice, blood and tissue samples were collected for PRL measurement by RIA, and pituitary PRL content, D2R and prolactin receptor long isoform (PRLR L) by real time PCR and Western blot (WB). Phospho-TH (p-THSer-40) expression was determined by WB in medial basal hypothalamus (MBH) extracts. Comparative CT method was used and RNA expression was normalized with respect to S16 gen (mean ± SEM; n: 6-8). Data were analyzed using two-way ANOVA and Student´s-t test. Serum PRL levels increased significantly in response to stress in male and OVX+E2 vs. control (SAL) rats, and PEA prevented this rise. E2 increased pituitary PRL expression (PCR) in basal and stressed conditions, and PEA reduced PRL content (WB) in OVX and OVX+E2 rats. Basal male D2R expression was lower than in females, and E2 treatment of OVX rats reduced D2R expression in PEA groups in terms of RNA and protein both in basal conditions and in response to stress. PEA and stress did not modify male PRLR L. However, stress reduced PRLR L expression in OVX and OVX+E2, and this effect was prevented by PEA. Moreover, stress reduced MBH p-TH in PEA OVX+E2 rats. In conclusion, prenatal amphetamine exposure may deregulate hypothalamus-pituitary axis, affecting PRL synthesis and secretion. E2 treatment may sensitize this effect.