Gonadotropin-releasing hormone (GnRH) neurons integrate synaptic information in their dendrites in order to precisely control GnRH secretion and hence fertility. Recent discoveries concerning the structure and function of GnRH neuron dendrites have shed new light on the control of GnRH neuron excitability and GnRH secretion. This work suggests that GnRH neurons have a unique projection to the m...

Gonadotropin-releasing hormone (GnRH) neurons integrate synaptic information in their dendrites in order to precisely control GnRH secretion and hence fertility. Recent discoveries concerning the structure and function of GnRH neuron dendrites have shed new light on the control of GnRH neuron excitability and GnRH secretion. This work suggests that GnRH neurons have a unique projection to the m...

BACKGROUND We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP). METHODS Infants admitted to the intensive care unit received a single ...

OBJECTIVE Phase 0 studies can provide initial pharmacokinetics (PKs) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of 2 antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standar...

BACKGROUND Antibodies against gonadotropin-releasing hormone (GnRH) and gastrointestinal dysmotility have been found after treatment with GnRH analogues. The aim of this study was to examine the presence of such antibodies in patients with dysmotility not subjected to GnRH treatment and study the anti-GnRH antibody effect on enteric neurons viability in vitro. METHODS Plasma and sera from 3 p...

The identification of gonadal gonadotropin-releasing hormone receptors (GnRH-R) and evidence of direct inhibitory effects of GnRH agonists upon steroidogenesis in adult rat gonads, lend credence to a putative intragonadal role of a locally secreted GnRH or GnRH-like peptide. Using reverse transcription-polymerase chain reaction followed by Southern blot hybridization and sequencing, we identifi...

Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with...

Intra-Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-lev...

Mammalian gonadotropin-releasing hormone (GnRH) receptors preferentially bind mammalian GnRH, which has Arg in position eight. The Glu(7.32(301)) residue, which determines selectivity of the mouse GnRH receptor for Arg(8)-containing GnRH, is Asp(7.32(302)) in the human GnRH receptor. We have confirmed that Asp(7.32(302)) confers selectivity of the human GnRH receptor for Arg(8) of GnRH and inve...

Gonadotropin-releasing hormone (GnRH) regulates the production of testosterone via the hypothalamic-pituitary-gonadal axis and testosterone, in turn, regulates the GnRH system via negative feedback. We compared testosterone regulation of GnRH mRNA expression in four anatomically defined GnRH cell groups in juvenile and adult male Syrian hamsters, including a rostral population of GnRH cells in ...