Sahlgrenska Osteoporosis Centre at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-405 30, Sweden.
Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg SE-413 45, Sweden.
Endocrinology. 2023 Jun 26;164(8). doi: 10.1210/endocr/bqad103.
Progesterone serum levels have been identified as a potential predictor for treatment effect in men with advanced prostate cancer, which is an androgen-driven disease. Although progesterone is the most abundant sex steroid in orchiectomized (ORX) male mice, the origins of progesterone in males are unclear. To determine the origins of progesterone and androgens, we first determined the effect of ORX, adrenalectomy (ADX), or both (ORX + ADX) on progesterone levels in multiple male mouse tissues. As expected, intratissue androgen levels were mainly testicular derived. Interestingly, progesterone levels remained high after ORX and ORX + ADX with the highest levels in white adipose tissue and in the gastrointestinal tract. High progesterone levels were observed in mouse chow and exceptionally high progesterone levels were observed in food items such as dairy, eggs, and beef, all derived from female animals of reproductive age. To determine if orally ingested progesterone contributes to tissue levels of progesterone in males, we treated ORX + ADX and sham mice with isotope-labeled progesterone or vehicle by oral gavage. We observed a significant uptake of labeled progesterone in white adipose tissue and prostate, suggesting that dietary progesterone may contribute to tissue levels of progesterone. In conclusion, although adrenal-derived progesterone contributes to intratissue progesterone levels in males, nonadrenal progesterone sources also contribute. We propose that dietary progesterone is absorbed and contributes to intratissue progesterone levels in male mice. We speculate that food with high progesterone content could be a significant source of progesterone in males, possibly with consequences for men undergoing androgen deprivation therapy for prostate cancer.
血清孕激素水平被认为是晚期前列腺癌男性治疗效果的潜在预测指标，而前列腺癌是一种雄激素依赖性疾病。虽然孕激素是去势（ORX）雄性小鼠中最丰富的甾体激素，但男性体内孕激素的来源尚不清楚。为了确定孕激素和雄激素的来源，我们首先确定了 ORX、肾上腺切除术（ADX）或两者（ORX+ADX）对多种雄性小鼠组织中孕激素水平的影响。正如预期的那样，组织内雄激素水平主要来源于睾丸。有趣的是，ORX 和 ORX+ADX 后孕激素水平仍然很高，其中白色脂肪组织和胃肠道中的孕激素水平最高。在鼠粮中观察到高孕激素水平，在乳制品、鸡蛋和牛肉等女性生殖期动物来源的食物中观察到异常高的孕激素水平。为了确定口服摄入的孕激素是否会导致雄性动物组织中的孕激素水平升高，我们通过口服灌胃用同位素标记的孕激素或载体治疗 ORX+ADX 和假手术小鼠。我们观察到标记的孕激素在白色脂肪组织和前列腺中的摄取明显增加，这表明饮食中的孕激素可能会导致组织中的孕激素水平升高。总之，尽管肾上腺源性孕激素有助于雄性动物组织内的孕激素水平，但非肾上腺源性孕激素来源也有贡献。我们提出，饮食中的孕激素被吸收并有助于雄性小鼠组织内的孕激素水平。我们推测，含有高孕激素含量的食物可能是男性体内孕激素的重要来源，这可能对接受前列腺癌雄激素剥夺治疗的男性产生影响。
