Adrenal (Excluding Mineralocorticoids)

ORF13-08 - Oxytocin as a Sex-Selective Regulator of Adrenal ACTH Sensitivity and Steroidogenic Response

Saturday, June 13, 2026

3:00 PM - 3:15 PM CT

Location: Room W183A

Oral Abstract Presenter(s)

AG

Anisa Gumerova, MD PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Stamford, New York, United States

Co-Author(s)

GP

Georgii Pevnev, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
UC

Uliana Cheliadinova, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
HK

Hasni Kannangara, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
GB

Guzel Burganova, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
OM

Ofer Moldavski, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
TF

Tal Frolinger, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
SS

Steven Sims, MS (he/him/his)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
KI

Kseniia Ievleva, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
VM

Valeriia Muradova, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
VL

Victoria Laurencin, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
PK

Pushkar Kumar, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
FK

Funda Korkmaz, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
ZN

Zahra Nakadar, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
DV

Darya Vasilyeva, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
JG

Judit Gimenez Roig, MS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
JR

Jensen Reckhow, MD (she/her/hers)

Reproductive Endocrinology and Infertility Fellow
Department of Obstetrics, Gynecology, and Reproductive Science, Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
FS

Farhath Sultana, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
OB

Orly Barak, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
VR

Vitaly Ryu, PhD (he/him/his)

Associate Professor
Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
RL

Rauf Latif, PhD

Associate Professor
Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
TY

Tony Yuen, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Senior Author/Primary Investigator(s)

MZ

Mone Zaidi, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Co-Author(s)

MZ

Mone Zaidi, MD PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Senior Author/Primary Investigator(s)

DL

Daria Lizneva, MD, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Co-Author(s)

DL

Daria Lizneva, MD, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Stress adaptation and glucocorticoid (GC) secretion are sexually dimorphic in mammals; however, the mechanisms underlying sex-specific adrenal responsiveness remain incompletely understood. Oxytocin (OXT) has been implicated in stress modulation, but its peripheral endocrine actions beyond parturition and lactation remain unclear. To determine whether OXT directly regulates adrenal steroidogenesis and contributes to sex-specific GC responses, we profiled Oxtr expression in mouse adrenal glands using qPCR, immunohistochemistry, and RNAscope in situ hybridization. Functional studies included ACTH- and OXT-stimulation assays in vivo and ex vivo, gain- and loss-of-function models, and bulk and single-cell RNA sequencing. To dissect central from peripheral actions, we generated adrenal-specific Star-CreERT2/Oxtrfl/fl and corticotroph-specific Pomc-Cre/Oxtrfl/fl mice. WT female mice exhibited markedly higher adrenal Oxtr expression relative to males and other tissues. RNAscope demonstrated co-localization of Oxtr and Mc2r in the zona fasciculata, suggesting integration of OXT and ACTH signaling at the level of GC-producing cells. Females displayed higher basal corticosterone levels and enhanced ACTH-stimulated GC responses. OXT injections for 5 days induced adrenal Oxtr, Cyp11b1, and Cyp19a1 upregulation and suppressed Cyp11b2 and Cyp21a1, consistent with steroidogenic pathway reprogramming. In primary adrenal cultures, OXT increased GC secretion. In Star-CreERT2/Oxtrfl/fl mice, Oxtr deletion in the adrenal attenuated ACTH-stimulated GC release and blunted stress-induced corticosterone elevations, accompanied by downregulation of key steroidogenic genes on bulk and single-cell RNAseq. Consistent with this, primary adrenal cells isolated from Star-CreERT2/Oxtrfl/fl mice confirmed cell-autonomous action, secreting significantly less corticosterone in response to OXT. A single OXT injection elicited a greater ACTH response in adrenal-specific Oxtr-deficient mice compared to controls; however, after 5 days of OXT treatment, corticosterone levels increased, whereas ACTH returned to baseline, consistent with the induction of a stress-like response followed by negative glucocorticoid feedback on ACTH secretion. Pomc-Cre/Oxtrfl/fl mice showed no difference from controls in basal or ACTH-stimulated GC or in response to OXT, indicating the adrenal as the dominant target of OXT action. Collectively, these findings position OXT as a female-biased regulator of adrenal steroidogenesis, acting through modulation of ACTH sensitivity and steroidogenic gene expression. These data indicate adrenal OXT-OXTR signaling as a previously unrecognized component of the stress axis and suggest a mechanistic framework for sex differences in HPA-axis physiology, with implications for pregnancy, postpartum endocrinology, and stress-related disorders.