FRI168 LH-hCG Receptor Is Expressed In All Three Zones Of Normal Adrenal Glands But Not In Aldosterone-Producing Micronodules

Abstract

Abstract Disclosure: S.A. Reda: None. A. Kirschenbaum: None. S. Yao: None. L. Milgram: None. J. Rege: None. A.C. Levine: None. Embryologically, the adrenals and gonads develop from the urogenital ridge with differential migration and differentiation. Post-natally, pituitary adrenocorticotropic hormone (ACTH) stimulates adrenal cortical cell growth and steroidogenesis, whereas pituitary luteinizing hormone (LH) regulates gonadal cell growth and steroidogenesis. However, there are multiple reports of gonadal tumorigenesis driven by high ACTH (in congenital adrenal hyperplasia) and adrenal cortical tumorigenesis driven by high LH/human chorionic gonadotropin (hCG) levels (adrenal tumors in pregnant and postmenopausal females). We studied the immunohistochemical expression of LH/hCG receptor (LH/hCG-R) in normal adrenal glands from 12 kidney donors (four male and eight female, two of which were <50 years of age and six were >50 years of age). Some of these specimens also contained aldosterone producing micronodules (APMs). Staining was performed for Synaptophysin, aldosterone synthase (CYP11B2), LH/hCG-R, WNT/β-Catenin, and DLK-1. In normal adrenal tissue, we first used synaptophysin stain to identify the nerves in the adrenal cortex as well as the adrenal medulla (M). CYP11B2 staining demonstrated immunoreactivity in a linear pattern throughout the Zona Glomerulosa (ZG) in five of the 12 samples. Faint expression of LH/hCG-R was detected in all twelve samples throughout the three layers of the adrenal cortex: the ZG, Zona Fasciculata (ZF) and Zona Reticularis (ZR). However, there were occasional cells in both the ZR and ZF that stained intensely for LH/hCG-R expression. LH/hCG-R immunoreactivity was also noted in the progenitor-rich subcapsular (SC) region. WNT β-Catenin, a transcription factor involved in the proliferation of adrenal cortical cells, stained most heavily in the SC/ZG region, possibly representing adrenal cortical progenitor cells. DLK-1, an adrenal cortical progenitor cell marker, was also expressed in the subcapsular zone. In adrenal tissues containing APMs, CYP11B2 immunostaining revealed areas of CYP11B2 positive cells that dip into the ZF, with no preserved linear staining for CYP11B2 in the ZG. LH/hCG-R stained most densely in the SC and ZG regions, with little to no immunoreactivity in the APMs. WNT β-Catenin likewise stained the SC and ZG regions with no expression in the APMs. Our findings suggests that LH/hCG-R is expressed sporadically in normal adrenal cortical tissue, but densely at times in all three zones of the adrenal cortex and the subcapsular area where the putative adult progenitor cells reside. The LH/hCG-R does not appear to be expressed throughout the entirety of APMs. Presentation: Friday, June 16, 2023