# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2020 · —

## Abstract

Numerous cross-sectional and longitudinal studies have established that circulating levels of testosterone
decline with age in men. Likewise, human aging also results in a gradual decline in ovarian steroid production,
a dramatic decline in adrenal androgens (DHEA, DHEAS), and alterations in cortisol and aldosterone
production and secretion. Similar to humans, aging in experimental rodents is also associated with profound
changes in the synthesis and secretion of steroid hormones, particularly testosterone. For the past 33 years or
so (with almost continuous support through Merit Review funding), my laboratory has been actively involved in
delineating cellular and molecular mechanisms involved in the age-related decline in steroid hormone
biosynthesis and secretion, with a particular emphasis on testosterone. Our work during the past several years
has established a causal link between increased reactive oxygen species formation/excessive oxidative stress
and oxidative damage to the cellular machinery involved in cholesterol transport to mitochondria resulting in
attenuated cholesterol transport with consequent impairment of steroidogenesis during aging. Currently, we
are investigating the impact of aging-induced excessive oxidative damage to cytosolic and mitochondrial
superoxide dismutase-peroxiredoxin (SOD-PRDX) antioxidant axes on the functional expression of crucial
proteins involved in cholesterol transport (SNAREs) to and within the mitochondria (StAR) for the production of
steroid precursor, pregnenolone. Over the years, a second major research effort of my laboratory has been
and continues to be to understand how cholesterol from lipoproteins, particularly, high-density lipoprotein
(HDL), is transported, processed intracellularly, and metabolized by steroidogenic tissues and cells. We are
also studying how this process affects steroid hormone synthesis, reverse cholesterol transport (RCT), and
atherosclerosis. Our work on HDL metabolism (funded by NIH since 1984), have led to the demonstration that
the cellular delivery of HDL-cholesteryl esters (CE) into steroidogenic cells does not involve the endocytic
pathway as typified by the LDL (B/E) receptor pathway. Rather, CE is taken into the cell via a `selective'
pathway in a process that did not require the internalization of the entire lipoprotein particle. This selective
pathway has been extensively characterized by us and it is especially important in liver and steroidogenic
tissues where it delivers CE in bulk for product formation (steroid and bile acids) and biliary cholesterol
secretion as a part of RCT. Scavenger receptor, class B type 1 (SR-B1) is an HDL receptor that mediates
selective delivery of HDL-CEs in steroidogenic and hepatic tissues and is also implicated in the
pathophysiology of RCT and atherosclerosis. At present, we are investigating the transcriptional and
posttranscriptional regulation of SR-B1 and its relevance to steroidogenesis, RCT, and atherosclerosis.
Currentl...

## Key facts

- **NIH application ID:** 9899086
- **Project number:** 5IK6BX004200-03
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** Salman Azhar
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899086

## Citation

> US National Institutes of Health, RePORTER application 9899086, BLR&D Research Career Scientist Award Application (5IK6BX004200-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899086. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*