Estrogen receptors and signaling pathways in lactotropes and somatotropes.

Estrogens are crucial determinants in the regulation of anterior pituitary function and maintenance of tissue homeostasis. Estrogen actions in this gland are exerted through both classical and non-classical mechanisms of action. This review summarizes the expression of classical α- and ß-estrogen receptors and variant isoforms of estrogen receptors in anterior pituitary cell subpopulations. We also analyze estrogen receptor signaling pathways involved in estrogenic actions in the anterior pituitary gland, especially in lactotropes and somatotropes. Complex interactions between multiple signaling pathways are involved in estrogen regulation of hormone secretion, cell proliferation and cell death in this gland. Insight into these pituitary responses to estrogens would help to understand pituitary function and tumorigenesis.

Morphological and morphometric changes of pituitary lactotrophs of viscacha (Lagostomus maximus maximus) in relation to reproductive cycle, age, and sex.

Lactotrophs in pituitary pars distalis (PD) of viscacha were studied by immunohistochemistry and morphometric analysis in the following groups: 1) adult males throughout the reproductive cycle (reproductive, gonadal regression, and recovery periods), 2) melatonin-treated adults, 3) castrated adults, 4) prepubertal, 5) non-pregnant females, and 6) pregnant females (early, mid, and late pregnancy). Immunopositive percentage area (%IA), cell percentage in PD (% PDC), number of cells per reference area (no.cell/RA), major cellular and nuclear diameters were analyzed. Lactotrophs were mainly localized in the ventro-medial region and the caudal extreme of PD. In the male viscachas, they were isolated in small and big groups, close to blood vessels and near follicles. These cells were pleomorphic and with a heterogeneous cytoplasmic immunolabeling pattern. In the adult males of the gonadal regression period the morphometric parameters were the lowest. Most parameters of lactotrophs in the prepubertal were significantly lower than in the adult males in the reproductive period. In the melatonin-treated animals and in castrated animals there was a decrease in %IA, %PDC, and no.cell/RA. In the females, the morphometric parameters increased at the end of pregnancy. Non-pregnant females exhibited a higher immunopositive area and number, but a smaller size of cells than males. Our results showed that in the adult male viscacha, lactotrophs vary seasonally, probably due to the photoperiod effect through melatonin. Besides the changes observed after castration, in prepubertal animals, in adults of different sex, and during pregnancy suggest that the gonadal steroid hormones might modify the lactotrophs activity.

Activation of PKC epsilon induces lactotroph proliferation through ERK1/2 in response to phorbol ester.

The aim of this investigation was to contribute to current knowledge about intracellular mechanisms that are involved in lactotroph cell proliferation, by evaluating the role of PKCalpha, PKCepsilon and extracellular-signal regulated kinase (ERK) 1/2 in response to phorbol 12-myristate13-acetate (PMA). In primary pituitary cultures, the activation of protein kinase C (PKC) by PMA for 15 min stimulated lactotroph proliferation; whereas a prolonged activation for 3-8h diminished this proliferative effect. The use of PMA for 15 min-activated PKCepsilon and ERK1/2, whereas incubation with PMA for 3 h induced PKCalpha activation and attenuated the PMA-triggered phosphorylation of ERK1/2. The following inhibitors: PKCs (bisindolylmaleimide I), PKCepsilon (epsilonV1 peptide) and ERK1/2 (PD98059) prevented the mitogenic activity induced by PMA for 15 min. Lactotroph cells stimulated with PMA for 15 min showed a translocation of PKCepsilon to membrane compartment and nucleus. These results thus establish that PKCepsilon plays an essential role in the lactotroph proliferation induced by PMA by triggering signals that involve ERK1/2 activation.