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Neuroendocrinology and Pituitary

ORF45-03 - Insights into Anterior Pituitary Cell Plasticity: Somatotrope-to-Lactotrope Transdifferentiation

Monday, June 15, 2026
2:15 PM - 2:30 PM CT
Location: Room W180
Disclosure(s):
Tiffany Miles, PhD: No financial relationships to disclose
Angela Odle, Ph.D.: No financial relationships to disclose

The anterior pituitary (AP) is a master endocrine organ controlling metabolism, reproduction, stress-response, and growth. Due to its strict size limitations within the sella turcica, the cellular composition and activity of the AP is vital to maintaining endocrine homeostasis. To maintain homeostasis, the AP response to endocrine demand is characterized by three distinct mechanisms: proliferation of terminal hormone-producing cells, recruitment of stem cells to generate hormone-producing cells, and transdifferentiation of hormone-producing cells. The activation and interplay of these mechanisms underlying pituitary cell plasticity are not fully understood. Importantly, it has been demonstrated that the AP is capable of responding to endocrine demand independent of terminal cell hyperplasia and stem cell differentiation. Transdifferentiation has been modelled with in vitro and in vivo responses to a variety of endocrine stressors including induction by growth factor cocktails, lactation, and hypothyroidism. The previously established method of GH3 rat somatotrope transdifferentiation combines insulin, 17β-estradiol, and epidermal growth factor (together, IBE) to induce somatrope-to-lactotrope transdifferentiation, confirmed through decreased levels of growth hormone (GH) peptide hormone and Gh1 mRNA, and increased levels of prolactin (PRL) peptide hormone and Prl mRNA. In this study, we have optimized IBE treatment of GH3 cells to generate an in vitro transdifferentiation model for mechanistic manipulation. Utilizing scRNAseq analysis across a 6-day time-course of IBE-treated GH3 cells, we have characterized a cluster of transdifferentiating cells and markers upregulated with IBE-treatment. Through proteogenomic analyses, we have identified key regulatory networks involved in somatotrope-to-lactotrope transdifferentiation and have evidenced conserved transcription factor activity profiles between this in vitro GH3 IBE somatotrope-to-lactotrope model and our separate in vivo mouse low iodine/propylthiouracil-diet induced somatotrope-to-thyrotrope transdifferentiation model. Our ongoing studies are designed to interdict the identified regulatory networks to control the direction and magnitude of the transdifferentiation response. We will present and discuss our findings on the roles of these candidates in mediating AP terminal cell transdifferentiation.