Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity

Polari, Lauri; Yatkin, Emrah; Martínez‐Chacón, Gabriela; Ahotupa, Markku; Smeds, Annika; Strauss, Leena; Zhang, F.; Poutanen, Matti; Saarinen, Niina M.; Mäkelä, Sari

doi:10.1016/j.mce.2015.06.002

Cited by 26 publications

(23 citation statements)

References 44 publications

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“…Interestingly, evidence in the literature points to CYP19 also being nutritionally regulated. CYP19-mediated conversion of testosterone to oestradiol is reduced in starved rodents (Seidl and Pirke, 1987), and obese patients have both increased oestradiol and measured testosteroneto-oestradiol conversion (Kley et al, 1980;Polari et al, 2015). This suggests that a similar nutrition-mediated steroid activation may function in regulating insulin output of mammals and warrants further investigation, particularly in the context of several human disorders with nutrition-associated phenotypes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone in Drosophila

et al. 2018

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Growth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues, such as nutritional status, is paramount for an orderly progression of development and growth. In Drosophila, this involves insulin and steroid signalling, but the underlying mechanisms and their coordination are incompletely understood. We show that bioactive 20-hydroxyecdysone production by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that under fed conditions, Shade plays a role in growth control. We identify the trachea and the insulin-producing cells in the brain as direct targets through which 20-hydroxyecdysone regulates insulin signalling. The identification of trachea-dependent regulation of insulin signalling exposes an important variable that may have been overlooked in other studies focusing on insulin signalling in Drosophila. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study insulin-producing cell function, and yield further insights into how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.

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Section: Discussionmentioning

confidence: 99%

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone in Drosophila

et al. 2018

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“…Aromatase belongs to the cytochrome P450 superfamily [18], which consists of 2 proteins: an NADPH-cytochrome P450 reduc-tase and a specific cytochrome P450 aromatase [16]. Aromatase is the rate-limiting enzyme and is responsible for the final step in the biosynthesis of estrogens from androgens; specifically, it transforms androstenedione and testosterone (T) into estrone and estradiol (E 2 ), respectively [22]. In humans, aromatase is expressed in many cells, including ovarian granulosa and luteal cells, testicular leydig and sertoli cells, placental cells, neurons, fibroblasts, vascular smooth muscle cells, preadipocytes, chondrocytes, and osteoblasts [18,23].…”

Section: Aromatase Gene Characteristics and Expressionmentioning

confidence: 99%

The Effect of Aromatase on the Reproductive Function of Obese Males

Sun

et al. 2017

Horm Metab Res

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Obesity has increased dramatically worldwide, which is associated with male infertility. Androgen deficiency, impaired spermatogenesis, and erectile dysfunction are characteristics of male infertility. The balance of androgens and estrogens is essential for maintaining normal reproductive function in males. Aromatase, the rate-limiting enzyme in the conversion of androgens into estrogens, is present in various tissues. The expression of aromatase is proportional to body fat mass and causes more fat accumulation, thus forming a vicious cycle. Excessive aromatase activity in adipose tissue leads to increased conversion of androgens into estrogens, eventually results in a reduction of testosterone levels and is the underlying reason for obesity-related infertility. In the male reproductive system, all testicular somatic cells and germ cells express aromatase, except for peritubular myoid cells. The results of studies regarding the effect of aromatase in testicular somatic cells and germ cells have been contradictory. The effect of estrogens in testicular somatic cells is inhibitory, leading to reduced testosterone levels and sperm production; however, it has been observed that aromatase participates in the acquisition of sperm motility. The overall effect of estrogen modulation is an inhibition of spermatogenesis. Aromatase inhibitors are an effective therapy for obesity-associated hypogonadism because they restore normal sex hormone levels and improve semen parameters. This article systematically introduces the basic knowledge of aromatase and provides information of the current advances relating to aromatase in male reproductive function. Increasing our knowledge on the role of aromatase in male obesity could help in proposing new approaches to treat infertile men.

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“…Interestingly, evidence in literature points to CYP19 also being nutritionally regulated. CYP19-mediated conversion of testosterone to estradiol is reduced in starved rodents (51), and obese patients have both increased estradiol and measured testosterone to estradiol conversion (52,53). This may imply that a similar nutrition-mediated steroid activation may function in regulating insulin output of mammals, and warrants further investigation particularly in the context of several human disorders with nutrition-associated phenotypes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone

Buhler

Clements

Winant

et al. 2017

Preprint

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Abbreviations: Dilps: Drosophila insulin-like peptides IPCs: Insulin-producing cells IIS: Insulin/Insulin-like growth factor signalling PG: Prothoracic Gland 20E: 20-hydroxyecdysone L1-L3: First, Second, Third Larval Instar FB: Fat Body RNAi: RNA interference qPCR: quantitative Polymerase Chain Reaction h AEL: hours after egg laying h AL3E: hours after third instar ecdysis 2 Abstract: Growth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues such as nutritional status is paramount for an orderly progression of development in function of growth. In Drosophila, this coordination involves insulin and steroid signalling, but the mechanisms by which this occurs and how they are coordinated are incompletely understood. We show that production of the bioactive 20-hydroxyecdysone by the enzyme Shade in the fat body is a nutrientdependent process. We demonstrate that during fed conditions, Shade plays a role in growth regulation, as knockdown of shade in the fat body resulted in growth defects and perturbed expression and release of the Drosophila insulin-like peptides from the insulinproducing cells (IPCs). We identify the trachea and IPCs as direct targets through which 20hydroxyecdysone regulates insulin-signaling. The identification of the trachea-dependent regulation of insulin-signaling exposes an important variable that may have been overlooked in other studies focusing on insulin-signaling in Drosophila. Finally, we show with IPCspecific manipulations that 20E may both be a growth-promoting and growth-inhibiting signal in the IPCs acting through different nuclear receptors. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study IPC function and yield further insights as to how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.3

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Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity

Cited by 26 publications

References 44 publications

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone in Drosophila

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone in Drosophila

The Effect of Aromatase on the Reproductive Function of Obese Males

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone

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