Endocrine Abstracts

Serum prolactin levels increase progressively from birth to adulthood in female and male rats, being higher in females from birth. Although this gradual increase was associated with concomitant maturation of prolactin-releasing and -inhibiting factors, these processes do not fully explain some sex differences observed. In in vitro studies, using lactotrophs in culture, from rats of different ages, in the absence of hypothalamic control, it was shown that the secretion of prolactin to the medium increases with age during the first weeks of life. These data suggest the involvement of intrapituitary factors. In the present work, the participation of pituitary activins, as paracrine factors, in the regulation of prolactin secretion during postnatal development was studied. Sex differences in this mechanism were also evaluated. Male and female Sprague Dawley rats aged 11, 23 and 45 days were used. Pituitary gene expression of activin subunits (Inhba and Inhbb) and activin receptors (ActRI, ActRIIA and ACTRIIB) was evaluated by RTqPCR. On day 11, female pituitary showed the highest expression of Inhba and Inhbb, being even significantly higher than that observed in males. The gene expression of activin subunits decreases with age in females, and the sexual differences disappears at 23 days. In contrast, the expression of Inhbb increases strongly at 45 days only in the pituitary glands of males, being the predominant activin subunit in this sex in adulthood. Gene expression of activin receptors (ActRIB, ActRIIA, and ACTRIIB) also decreases in females during postnatal development, while remaining relatively stable in males. We also evaluated the protein expression of ActRIB and its co-location with PRL. The proportion of lactotrophs (PRL+) expressing the receptor (ActRIB+) is highest in the pituitary glands of 11-day-old females and decreases with age. Activins have been described to inhibit PRL synthesis by inhibiting the transcription factor Pit-1 (or Pou1f1). This action not only involves the canonical pSMAD pathway, but also the phosphorylation of p38MAPK. At p11 almost all lactotrophs express p-p38MAPK in females, and its expression decreases with age with a concomitant increase in Pit-1. Our findings suggest that: the inhibitory regulation of pituitary activins on prolactin secretion is sex-specific; this regulation is more relevant in females during the first week of life and decreases with age; this intra-pituitary regulation is involved in the sex-differences observed in serum prolactin levels during postnatal development.