5 research outputs found
Splicing analysis of CYP11B1 mutation in a family affected with 11β-hydroxylase deficiency: case report
Effects of endocrine disruptors on adreno-cortical and Leydig cell steroidogenesis
A common sequential pathway for steroidogenesis, designed to produce
steroid hormones, is expressed in the adrenal cortex, testes and ovaries.
In this process, cholesterol is converted to all known steroids by
specific enzymes in a tissue-specific manner. In addition to the
maintenance of reproduction, fertility and normal sexual development by
androgens and estrogens, mineralocorticoids and glucocorticoids, other
steroids produced by the adrenal cortex, play important roles in the
regulation of salt balance and responses to stress, respectively.
Steroidogenesis is controlled by interactions between the hypothalamus
and pituitary in the form of a negative feedback loop, and, disruption of
any step in this loop exerts an impact on the entire axis.
In recent years, numerous anthropogenic or naturally occurring compounds
in the environment have been reported to influence the homeostasis of
endocrine systems. These xenobiotics, referred to as endocrine disrupting
chemicals (EDCs), may disrupt the development and/or functioning of
various physiological systems, including reproduction, fertility, sexual
differentiation and stress responses, both in wildlife and humans. Such
disruption may be involved in the increased incidences of testicular
cancer, hypospadias and cryptorchidism, as well as the decline in sperm
count observed in humans during the past decades. Accordingly, the aim of
the present thesis was to explore the effects of several xenobiotics
(i.e., the anti-androgen procymidone, the phytoestrogens genistein and
resveratrol, and sesquiterpene lactone helenalin and phthalates) on the
function of the pituitary-gonadal and pituitary-adrenal axes and the
biosynthesis of sex steroids and glucocorticoids, employing in vitro and
ex vivo cultures of rat Leydig and adrenocortical cells as a model
system.
Dietary administration of procymidone to male rats resulted in elevated
serum levels of luteinizing hormone (LH) and testosterone. Furthermore,
Leydig cells isolated from these animals displayed an enhanced capacity
for the production of testosterone in response to stimulation by human
chorionic gonadotropin (hCG) or (Bu)2cAMP, as well as elevated expression
of steroidogenic acute regulatory (StAR) protein, cytochrome P450scc
(P450scc) and cytochrome P450c17 (P450c17). In contrast, diets containing
genistein inhibited the ex vivo steroidogenic response of Leydig cells to
hCG or (Bu)2cAMP by down-regulating their expression of P450scc. In a
similar manner, phytoestrogen resveratrol suppressed corticosterone
production by primary cultures of adrenocortical cells both in vitro and
ex vivo in association with a decrease in the expression of cytochrome
P450 c21-hydroxylase. Helenalin, a sesquiterpene lactone produced by
several species of the Asteracea family of plants, inhibited both
adrenocorticotropic hormone (ACTH) - and hCG-activated steroidogenesis in
primary cultures of rat adrenocortical and Leydig cells as a result of
attenuated expression of the StAR protein, which mediates cholesterol
transport into mitochondria.
Further experiments demonstrated that administration of di-2-ethylhexyl
phthalate (DEHP) to male rats causes age-dependent alterations in their
pituitary-adrenocortical axis in vivo and adrenocortical steroidogenesis
ex vivo. Thus oral exposure to this phthalate ester elevated serum levels
of ACTH and corticosterone in rats 20 and 40 days of age, but not in
adult, 60-day-old animals. In addition, primary cultures of
adrenocortical cells isolated from the two younger groups of rats treated
with DEHP exhibited enhanced production of corticosterone in response to
stimulators, as well as elevated ACTH-stimulated transport of endogenous
cholesterol into mitochondria.
Together, these findings reveal that the EDCs examined can influence the
function and regulation of the pituitary-gonadal and pituitary-adrenal
axes in rats, as well as impair their adrenocortical and Leydig cell
steroidogenesis by suppressing the expression of several proteins
involved in steroidogenesis (e.g., StAR, P450c21 and P450scc). Such
effects might disrupt reproductive potential, fertility and homeostasis
in both humans and wildlife
DKA with Severe Hypertriglyceridemia and Cerebral Edema in an Adolescent Boy: A Case Study and Review of the Literature
A 13-year-old adolescent boy with type 1 diabetes mellitus (1b) presented with diabetic ketoacidosis (DKA) and cerebral edema. Grossly lipemic serum and lipemia retinals due to extremely high triglyceride (TG) level were observed without evidence of xanthoma or xanthelasma. Cerebral edema was treated by appropriate ventilation and mannitol administration. Normal saline was carefully given and regular insulin was titrated according to blood sugar levels. Triglyceride levels were reduced from 9,800 mg/dL to normal range within 9 days after conventional treatment was commenced without antilipid medication. Based on our review of the literature, this is the first reported case of confirmed pediatric DKA with severe hypertriglyceridemia and cerebral edema. In patients with DKA and hypertriglyceridemia, clinicians should be mindful of the possibility of associated acute pancreatitis and cerebral edema
Exposure to Bisphenol A and Its Analogs among Thai School-Age Children
Bisphenol F (BPF) and bisphenol S (BPS) have become popular substitutes for bisphenol A (BPA) in the plastic industry due to concerns over BPA’s adverse effects. However, there is limited information on children’s exposure to these chemicals. This study aims to assess the extent of BPA, BPF, and BPS exposure and determine factors that influence such exposure. A group of Thai children (age 6–13 years, N = 358) were recruited between October 2019 and 2020. Two first-morning voids were collected one week apart. Demographic and exposure-related information was gathered. Urinary concentrations of bisphenols were analyzed by liquid chromatography and tandem mass spectrometry. Correlation between bisphenol concentrations with age, body weight, and sources of bisphenol exposure, was determined using generalized estimating equations with linear model. BPA, BPF, and BPS were detected at 79.6%, 31.0%, and 16.8%, with geometric mean (GM) concentrations of 1.41, 0.013, and 0.014 ng/mL, respectively. Younger children aged <10 years exhibited 1.3–1.6 times higher GM levels of all bisphenols compared to older children. Exposure to food stored in plastic containers was associated with higher levels of BPF and BPS. In conclusion, BPA was the most frequently detected bisphenol in urine samples from Thai children, followed by BPF and BPS