Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

Abstract

Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record

The Disruptive Effects of Estrogen Removal Before Puberty on Risk for Binge Eating in Female Rats

“…The distribution of binge eating in the BER/BEP model also resembles that observed in women becuase there is a continuum of binge eating (from low to high levels), but the model also identifies rats that are particularly resistant or prone to binge eating (Boggiano et al, 2007). Finally, more female rats than male rats are categorized BEP, and BEP phenotypes emerge during puberty (Culbert, Sinclair, et al, 2018; Klump, Suisman, Culbert, Kashy, & Sisk, 2011).…”

“…Past studies have frequently used a 50% to 67% criterion for defining “consistent” intake (e.g., BEP rats had to consume in the highest tertile in three of six feeding tests (50%) and never in the lowest tertile; Culbert, Sinclair, et al, 2018; Hildebrandt, Klump, Racine, & Sisk, 2014; Klump, Racine, Hildebrandt, & Sisk, 2013; Klump, Suisman, Culbert, Kashy, & Sisk, 2011; Sinclair et al, 2015). We used a similar definition and required that rats consume in the highest or lowest tertile of PF intake on 57% to 67% of the adult feeding tests to meet our BEP and BER criteria, respectively.…”

“…However, emerging data indicate that these protective effects are not present earlier in development (Asarian & Geary, 2013; Klump, Culbert, & Sisk, 2017). For example, exogenous estradiol treatment fails to alter chow intake in prepubertal female rats (Asarian & Geary, 2013), and differences in PF intake among female rats that are prone as opposed to resistant to binge eating emerge only during mid-late puberty (Culbert, Sinclair, Hildebrandt, Klump, & Sisk, 2018; Klump, Suisman, Culbert, Kashy, & Sisk, 2011). Likewise, although rates of binge eating increase during mid-late puberty in girls, there are minimal associations between estradiol levels and binge eating before adulthood (Harden et al, 2014; Klump, 2013; Klump et al, 2018; Klump, Keel, Sisk, & Burt, 2010).…”

“…Animal studies are ideal for examining these influences because ovarian hormones can be directly manipulated to test effects on behavior. One promising model is the BER/BEP rat model (Boggiano et al, 2007) that has been used in previous studies of activational/organizational hormone effects (Culbert, Sinclair, et al, 2018; Klump, Suisman, Culbert, Kashy, Keel, & Sisk, 2011; Klump, Suisman, Culbert, Kashy, & Sisk, 2011). This model identifies BER and BEP female rats on the basis of their consumption of intermittently presented, highly PF in adulthood and shows good face validity for the binge eating that occurs in binge-eating-related disorders (i.e., binge-eating disorder, or BED; bulimia nervosa, or BN) in women (see Method section for additional information on model validity).…”

Reduced Medial Prefrontal Control of Palatable Food Consumption Is Associated With Binge Eating Proneness in Female Rats

“…For both cohorts, feeding tests for experiment 1 began after 1 week of acclimation to housing conditions at our facility, so all testing in each cohort began on postnatal day 67. Feeding tests were run in two separate cohorts of rats and were conducted using a protocol adapted from one that has been used previously in our lab (Klump et al, 2011a, b, 2013; Hildebrandt et al, 2014; Sinclair et al, 2015; Culbert et al, 2018). Feeding tests were conducted over a period of 2 weeks and included six total feeding test days.…”