FOXO transcription factors are required for normal somatotrope function and growth

Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum IGF1 levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.

Morphological and Functional Changes of Pituitary GH and PRL Cells Following Prolonged Exposure of Female Rats to Constant Light

Light regulates numerous physiological functions including secretion of different hormones. Our aim was to determine morphological and functional changes of the pituitary growth hormone (GH) and prolactin (PRL) producing cells in female rats exposed to constant light regime from the peripubertal to adult period of life. Starting from the thirtieth postnatal day, female Wistar rats were exposed to constant light (600 lx) for the following 95 days. Controls were maintained under the regular laboratory lighting conditions. The GH and PRL cells were immunohistochemically visualized. Changes in cell volumes and volume densities were evaluated by stereology. Concentrations of PRL and GH in circulation were also determined. We detected significant decrease of the GH cell volume and volume density, followed by reduced the GH blood concentration in comparison to the controls. In contrast, PRL cells were larger in size and their volume density was significantly increased when compared to the controls. Accordingly, PRL concentration was elevated. It can be concluded that exposure of female rats to constant light regime, from peripubertal to adult period of life, causes inhibition of the pituitary GH and stimulation of PRL cells.

VENUS BY BOTTICELLI AND HER PITUITARY ADENOMA

Objective: Simonetta Vespucci, considered the most beautiful woman of the Renaissance, is the inspiration and face of one of the most famous paintings of all times, “The Birth of Venus,” by Botticelli. She died in 1476 at the age of 23 years. We postulate she suffered from a pituitary-secreting tumor progressing to pituitary apoplexy. The goals of this study were 3-fold: (i) verify that the subject depicted by Botticelli in different paintings represents the same woman; (ii) identify the facial traits affected by the progression of a growth hormone– and prolactin-secreting tumor; and (iii) confirm that the observed changes of the face traits observed in the portraits of Simonetta Vespucci are compatible with the facial traits changes identified earlier. Methods: Comparison among face traits was based on the analysis of the face regions measured by means of fiducial points and their distances, and after pose compensation based on three-dimensional head modelling. Results: In favor of the hypothesis that Simonetta suffered from a pituitary growth hormone– and prolactin-secreting tumor stands changes of her lineaments, a feature which becomes evident over the years and particularly manifest in the Allegorical Lady, where galactorrhea is depicted. Conclusion: We conclude that sufficient evidence is presented to suggest that Simonetta Vespucci, the Venus depicted by Botticelli, suffered from pituitary adenoma secreting prolactin and growth hormon with parasellar expansion. The current interpretation of the Venus strabism should be revisited according to this finding. Abbreviation: GH = growth hormone