We have prepared fresh pituitary gland slices from adult and, for the first time, from newborn mice to assess modulation of secretory activity via voltage-activated Ca²⁺ channels (VACCs). Currents through VACCs and membrane capacitance have been measured by a whole-cell patch-clamp. Melanotrophs in newborns were significantly larger than in adults. In both newborn and adult melanotrophs activation of VACCs triggered exocytosis. All pharmacologically isolated VACC types contributed equally to the secretory activity. However, the relative proportion of VACCs differed between newborns and adults. In newborn cells L-type channels dominated and, in addition, an exclusive expression of a toxin-resistant R-type-like current was found. The expression of L-type VACCs was upregulated by the increased estrogen levels observed in females, and even more emphasized in the cells of pregnant females and estrogen-treated adult male mice. We suggest a general mechanism modulating endocrine secretion in the presence of estrogen and particular higher sensitivity to treatments with L-type channel blockers during high estrogen physiological states.