Gonadotrope Remodeling in Sustained Low Estrogen States: Single-Cell Transcriptomic Analysis Reveals Gonadotrope Subtypes and Activation of Stem Cell Populations.

Both gonadotrope clusters showed upregulated genes for canonical pathways supporting mRNA translation and secretion, which correlated well with the high serum gonadotropin levels. However, the LH beta subunit (Lhb) transcript was unchanged and FSH beta subunit (Fshb) was significantly reduced, suggesting that the high gonadotropin secretion may be supported by post-transcriptional regulators. The pituitary Sox2-positive (Sox2) stem cell cluster exhibited increased expression of Sox9, a marker for more mature transitional progenitors, and showed upregulation of pathways involved in stem cell development, mitotic activity, and mRNA translation.

This model provides insight into the cellular and molecular adaptations of the gonadotropes and their progenitor cells to the low estrogen/menopausal state, with potential relevance for understanding human perimenopausal and menopausal physiology.