Obesity and Sex Steroid Changes across Puberty: Evidence for Marked Hyperandrogenemia in Pre- and Early Pubertal Obese Girls

University of California, San Diego, San Diego, California, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 02/2007; 92(2):430-6. DOI: 10.1210/jc.2006-2002
Source: PubMed


Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear.
The objective of the study was to assess the degree of hyperandrogenemia across puberty in obese girls and assess overnight sex steroid changes in Tanner stage 1-3 girls.
This was a cross-sectional analysis.
The study was conducted at general clinical research centers.
Thirty normal-weight (body mass index for age < 85%) and 74 obese (body mass index for age >or= 95%) peripubertal girls.
Blood samples (circa 0500-0700 h) were taken while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1-3 girls.
Hormone concentrations stratified by Tanner stage were measured.
Compared with normal-weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, whereas fasting insulin was 3-fold elevated in obese Tanner 1-3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05) but not in more mature girls. In a subgroup of normal-weight Tanner 1-3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P <or= 0.001). In obese Tanner 1-3 girls (n = 6), evening P and T were elevated, and both tended to increase overnight [mean 1.4- and 1.6-fold, respectively (P = 0.06)].
Peripubertal obesity is associated with hyperandrogenemia and hyperinsulinemia throughout puberty, being especially marked shortly before and during early puberty. P and T concentrations in normal-weight Tanner 1-3 girls increase overnight, with similar but less evident changes in obese girls.

13 Reads
  • Source
    • "ontribute to the development and manifestation of PCOS ( Goodarzi et al . 2011 ; Pasquali et al . 2011 ) . Previous studies conducted in humans and animals suggest that the exposure of females to androgen during early life ( prenatal , perinatal or early postnatal life ) may lead to appearance of PCOS phenotype in adulthood ( Ibáñez et al . 2000 ; McCartney et al . 2007 ; Wu et al . 2010 ) . Production of an animal model that mimics many features of PCOS could contribute to a better understanding of the aetiology and the cellular and molecular mechanisms underlying the pathophysiology of PCOS , and also aid in detection of therapeutic methods for this syndrome . Sheep and non - human primates with some"
    [Show abstract] [Hide abstract]
    ABSTRACT: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, with a prevalence of 8-12% during the reproductive years. In the current study using prenatal exposure to a single dose of testosterone during the critical period of fetal development, we aimed to introduce an enhanced rat model which would exhibit both endocrine and ovarian disturbances similar to PCOS, while maintaining a normal reproductive system morphology in adulthood. Ten pregnant rats were subcutaneously injected with 5 mg free testosterone on gestational day 20, while control rats received only solvent. Development and function of the reproductive system in female offspring were examined in adulthood. Prenatally androgenized offspring had irregular estrous cycles compared to controls and their anogenital and anovaginal distances were increased compared to controls (p<0.001). No significant differences were observed in vaginal and clitoris lengths or the number of nipples between the two groups. Levels of testosterone and LH and also LH/FSH ratio were increased in prenatally androgenized offspring, compared to controls (p<0.05). The number of preantral and antral follicles in the ovaries of prenatally androgenized offspring was also increased compared to controls (p=0.07 and p<0.01, respectively). The number of corpora lutea was decreased in prenatally androgenized offspring compared to controls. Cystic follicles were observed in the ovaries of prenatally androgenized offspring. Prenatal exposure to a single dose of testosterone during the critical period of fetal development could facilitate the development a functional rat model of PCOS in adulthood, with minimum morphological disorders in the reproductive system.
    Experimental physiology 02/2014; 99(5). DOI:10.1113/expphysiol.2014.078055 · 2.67 Impact Factor
  • Source
    • "In addition, THP can be produced de novo in the brain from cholesterol via side chain cleavage enzyme (Compagnone and Mellon, 2000) in several CNS sites, including the CA1 hippocampal pyramidal cell (Agis-Balboa et al., 2006). Circulating and/or CNS levels of this steroid increase before puberty, but decline to low levels at the onset of puberty, (Fadalti et al., 1999; McCartney et al., 2007; Shen et al., 2007). Unlike most steroids, THP has no known effect at classic nuclear steroid receptors, but instead is a modulator of the GABAR (Smith et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The onset of puberty is associated with alterations in mood as well as changes in cognitive function, which can be more pronounced in females. Puberty onset in female mice is associated with increased expression of α4βδ γ-amino-butyric acid-A (GABAA) receptors (GABARs) in CA1 hippocampus. These receptors, which normally have low expression in this central nervous system (CNS) site, emerge along the apical dendrites as well as on the dendritic spines of pyramidal neurons, adjacent to excitatory synapses where they underlie a tonic inhibition that shunts excitatory current and impairs activation of N-methyl-D-aspartate (NMDA) receptors, the trigger for synaptic plasticity. As would be expected, α4βδ expression at puberty also prevents long-term potentiation (LTP), an in vitro model of learning which is a function of network activity, induced by theta burst stimulation of the Schaffer collaterals to the CA1 hippocampus. The expression of these receptors also impairs spatial learning in a hippocampal-dependent task. These impairments are not seen in δ knock-out (-/-) mice, implicating α4βδ GABARs. α4βδ GABARs are also a sensitive target for steroids such as THP ([allo]pregnanolone or 3α-OH-5α[β]-pregnan-20-one), which are dependent upon the polarity of GABAergic current. It is well-known that THP can increase depolarizing current gated by α4βδ GABARs, but more recent data suggest that THP can reduce hyperpolarizing current by accelerating receptor desensitization. At puberty, THP reduces the hyperpolarizing GABAergic current, which removes the shunting inhibition that impairs synaptic plasticity and learning at this time. However, THP, a stress steroid, also increases anxiety, via its action at α4βδ GABARs because it is not seen in δ(-/-) mice. These findings will be discussed as well as their relevance to changes in mood and cognition at puberty, which can be a critical period for certain types of learning and when anxiety disorders and mood swings can emerge.
    Frontiers in Neural Circuits 09/2013; 7:135. DOI:10.3389/fncir.2013.00135 · 3.60 Impact Factor
  • Source
    • "In addition, peripubertal obesity has been described to reduce sex hormone binding globulin (SHBG) levels, which in turn increase the bioavailability of sex steroids including estradiol.32,47 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Childhood obesity is a growing and alarming problem, associated with several short-term and long-term metabolic and cardiovascular complications. In addition, it has also been suggested that excess adiposity during childhood influences growth and pubertal development. Several studies have shown that during pre-pubertal years, obese patients present higher growth velocity and that this pre-pubertal advantage tends to gradually decrease during puberty, leading to similar final heights between obese and non-obese children. Excess body weight might also influence pubertal onset, leading to earlier timing of puberty in girls. In addition, obese girls are at increased risk of hyperandrogenism and polycystic ovary syndrome. In boys, a clear evidence does not exist: some studies suggesting an earlier puberty associated with the obesity status, whereas other have found a delayed pubertal onset. Overall, the existing evidence of an association between obesity and modification of growth and pubertal patterns underlines a further reason for fighting the epidemics of childhood obesity.
    Pediatric reports 12/2012; 4(4):e35. DOI:10.4081/pr.2012.e35
Show more

Preview (2 Sources)

13 Reads
Available from