Akin, Senay, Metin Bastug, Ridvan Colak, Hakan Ficicilar, Betul Simten Saglam, Nazan S. Kosar, and Haydar Demirel. Possible adaptation of the adrenal gland Hsp72 expression to hypoxic stress. High Alt Med Biol. 00:000-000, 2021. Background: Adrenal glands play a central role in the general response to stress and controlling wholebody homeostasis. One of the most severe environmental stresses encountered by high-altitude climbers is hypoxia. Since the 72 kDa heat shock protein (Hsp72) has a critical role in cellular homeostasis, regulation of Hsp72 in adrenal glands seems to be crucial for maintaining cellular integrity of the gland and sustaining an adequate whole-body stress response in a hypoxic environment. Therefore, this study investigated if 15 days of hypoxia results in the induction of Hsp72 in adrenal glands. In addition, we examined whether heat treatment had any effect on adrenal Hsp72 expression to hypoxia, as cellular and systemic physiological cross-adaptation was suggested between heat stress and hypoxic stress. Materials and Methods: Male 4-month-old Wistar rats were randomly assigned to one of the four experimental groups (n = 8 each group): (1) control (C), (2) heat treatment (15H), (3) heat treatment and 15 days of normobaric hypoxia (15HHp), and (4) 15 days of normobaric hypoxia (15Hp). Three one-hour heat treatment sessions at 41 degrees C were applied on the first two days before hypoxic exposure and on the day 7. Hypoxic exposure was consisting of normobaric hypoxia containing 9.7% O-2. Results: Fifteen days of hypoxia did not increase the adrenal Hsp72 levels (p = 0.99). Furthermore, when hypoxia was added to the heat treatment, heat-related increases in adrenal Hsp72 levels disappeared. Adrenal weight to body weight ratio was not different among groups (p = 0.11). Plasma corticosterone levels were significantly lower in all experimental groups compared with control (p < 0.05), and addition of hypoxia resulted in further significant reduction of the plasma corticosterone levels (C > 15H>15HHp >15Hp; p < 0.05). Conclusions: These data demonstrate the adaptation of the adrenal gland to 15-day chronic normobaric hypoxic stress as well as possible cross-adaptation between heat and hypoxic stress in the adrenal gland.