Effect of Glucocorticoid-Induced Insulin Resistance on Follicle Development and Ovulation

Abstract

Polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenemia, polycystic ovaries, and menstrual disturbance and a clear association with insulin resistance. This research evaluated whether induction of insulin resistance, using dexamethasone (DEX), in a monovular animal model, the cow, could produce an ovarian phenotype similar to PCOS. In all of these experiments, DEX induced insulin resistance in cows as shown by increased glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). Experiment 1: DEX induced anovulation (zero of five DEX vs. four of four control cows ovulated) and decreased circulating estradiol (E2). Experiment 2: Gonadotropin-releasing hormone (GnRH) was administered to determine pituitary and follicular responses during insulin resistance. GnRH induced a luteinizing hormone (LH) surge and ovulation in both DEX (seven of seven) and control (seven of seven) cows. Experiment 3: E2 was administered to determine hypothalamic responsiveness after induction of an E2 surge in DEX (eight of eight) and control (eight of eight) cows. An LH surge was induced in control (eight of eight) but not DEX (zero of eight) cows. All control (eight of eight) but only two of eight DEX cows ovulated within 60 h of E2 administration. Experiment 4: Short-term DEX was initiated 24 h after induced luteal regression to determine if DEX could acutely block ovulation before peak insulin resistance was induced, similar to progesterone (P4). All control (five of five), no P4-treated (zero of six), and 50% of DEX-treated (three of six) cows ovulated by 96 h after luteal regression. All anovular cows had reduced circulating E2. These data are consistent with DEX creating a lesion in hypothalamic positive feedback to E2 without altering pituitary responsiveness to GnRH or ovulatory responsiveness of follicles to LH. It remains to be determined if the considerable insulin resistance and the reduced follicular E2 production induced by DEX had any physiological importance in the induction of anovulation.

Relationship between the indexes of insulin resistance and metabolic status in dairy cows during early lactation

“…Cows in the experiment obtained by Haarstrich were in day 182 of lactation, meaning in a later lactation period compared to our cows. Hackbart and coworkers (2013) [11] showed effects of dexamethasone on insulin resistance since HOMA index value was 5.0±1.0 before and 15.0±2.5 after application of dexamethasone.…”

“…Classifi cation of cows on quartiles did not show signifi cant results because of physiologically high variations of cortisol concentrations. Application of dexamethasone leads to greater insulin resistance [11]. Well known fact is that healthy people that were treated with dexamethasone show insulin resistance.…”

“…These adaptations are increased lipid mobilization, ketogenesis and lipid oxidation [6][7][8], reduced levels of thyroid hormones [9], changed STH to IGF-I ratio [10], increased levels of cortisol [11], changes in hepatic insulin receptors abundance, increased activity of hepatic enzymes [6,12,13] and reduced concentration of Ca and P [14,15]. However, there is a lack of literature data related to the direct relationship between the value of the indexes of insulin resistance and metabolic or endocrine parameters.…”

Associations of insulin resistance later in lactation on fertility of dairy cows

“…However, late-lactation cows had decreased rates of both cleavage (P ¼ 0.08) and blastocyst formation (P ¼ 0.0005). In addition to fewer embryos produced, late-lactation cows had greater peripheral insulin resistance than early-lactation cows, based on homeostasis model assessment of insulin resistance (HOMA-IR; Table 1 [38,39]). The HOMA-IR was calculated according to a formula presented in the previous studies [38,39]: Fig.…”

Produção embrionária, perfil endócrino, metabólico e molecular de vacas holandesas não-lactantes recebendo dieta à base de milho ou polpa cítrica

“…Ela ocorre em vacas no período pós-parto imediato (BELL; BAUMAN, 1997), em vacas leiteiras no pós-parto ingerindo quantidades insuficientes de energia e apresentando altas concentrações circulantes de AGNEs (PIRES; PESCARA; GRUMMER, 2007), em vacas lactantes ou não recebendo dieta altamente energética sem a suplementação de propionato de cromo (LEIVA et al, 2013(LEIVA et al, , 2014(LEIVA et al, , 2015, com o avançar da lactação (aos 150 dias em leite; OLIVEIRA et al, 2016), após ingestão prolongada de dietas de alta energia por vacas não lactantes (SALES et al, 2015), em vacas gestantes e não lactantes sobrepeso (DE KOSTER et al, 2015) e após o tratamento com glicocorticoides (HACKBART et al, 2013).…”