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Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH) which activates specific receptors (GnRHR) present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. How the physiological fluctuations of GnRH secretion that orchestrate normal reproduction are decoded by the gonadotrope cell machinery to ultimately control gonadotropin release and/or subunit gene transcription has been the subject of intensive studies during the past decades. Surprisingly, the mammalian GnRHR is unique among G protein-coupled receptor family as it lacks the carboxy-terminal tail usually involved in classical endocytotic process. Accordingly, it does not desensitize properly and internalizes very poorly. Both this atypical intrinsic property and post-receptor events may thus contribute to decode the GnRH signal. This includes the participation of a network of signaling pathways that differently respond to GnRH together with a growing amount of genes differentially sensitive to pulse frequency. Among these are two pairs of genes, the transcription factors EGR-1 and NAB, and the regulatory factors activin and follistatin, that function as intracellular autoregulatory feedback loops controlling respectively LHβ and FSHβ gene expression and hence, LH and FSH synthesis. Pituitary gonadotropes thus represent a unique model of cells functionally adapted to respond to a considerably fluctuating neuroendocrine stimulation, from short individual pulses to sustained GnRH as observed at the proestrus of ovarian cycle. Altogether, the data emphasize the adaptative reciprocal complementarity of hypothalamic GnRH neurones and pituitary gonadotropes to function as an original unit. [ABSTRACT FROM AUTHOR]

Background Objectives Results and Discussion In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle, which contains dynein motor proteins that provide the mechanical force for sperm propulsion and motility. Primary motility of the sperm cells is acquired during their transit through the epididymis and hyperactivated motility is acquired throughout the journey in the female genital tract by a process called capacitation. These activation processes rely on the micro‐environment of the genital tracts. In particular, during capacitation, a panoply of ion transporters located at the surface of the sperm cells mediate complex ion exchanges, which induce an increase in plasma membrane fluidity, the alkalinization of the cytoplasm and protein phosphorylation cascades that are compulsory for sperm hyperactivation and fertilization potential. As a consequence, both structural and functional defects of the sperm flagellum can affect sperm motility, resulting in asthenozoospermia, which constitutes the most predominant pathological condition associated with human male infertility.Herein, we have performed a literature review to provide a comprehensive description of the recent advances in the genetics of human asthenozoospermia.We describe the currently knowledge on gene mutations that affect sperm morphology and motility, namely, asthenoteratozoospermia; we also specify the gene mutations that exclusively affect sperm function and activation, resulting in functional asthenozoospermia. We discuss the benefit of this knowledge for patient and couple management, in terms of genetic counselling and diagnosis of male infertility as a sole phenotype or in association with ciliary defects. Last, we discuss the current strategies that have been initiated for the development of potential therapeutical and contraceptive strategies targeting genes that are essential for sperm function and activation. [ABSTRACT FROM AUTHOR]

Glucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC signaling in gonadotrope cells triggered by a membrane-associated GR. Herein, we demonstrate the existence of a specific membrane-initiated GC signaling in LβT2 gonadotrope cells involving two related phosphoproteins: Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII) and synapsin-I. Within 5 min, LβT2 cells treated with stress range of 10 -7  M Corticosterone or a membrane impermeable-GC, BSA-conjugated corticosterone, exhibited a 2-fold increase in levels of phospho-CaMKII and phospho-synapsin-I. Biochemical approaches revealed that this rapid signaling is promoted by a palmitoylated GR. Importantly, GC significantly alter GnRH-induced CaMKII phosphorylation, consistent with a novel cross-talk between the GnRH receptor and GC. This negative effect of GC on GnRH signaling was further observed on LH release by mouse pituitary explants. Altogether, our work provides new findings in GC field by bringing novel understanding on how GR integrates plasma membrane, allowing GC membrane-initiated signaling that differs in presence of GnRH to disrupt GnRH-dependent signaling and LH secretion.

The activity of pituitary gonadotrope cells, crucial for reproductive function, is regulated by numerous factors including signals related to nutritional status. In this work, we demonstrated, for the first time, that in vivo central exposure of rats to lipids intracarotid infusion of a heparinized triglyceride emulsion selectively increases the expression of pituitary LH subunit genes without any alteration of pituitary GnRH receptor and hypothalamic GnRH or Kiss-1 transcript levels. Furthermore, we showed that unsaturated fatty acids (UFA), oleate and linoleate, increase LH release in a dose-dependent manner as well as LHβ mRNA levels in both immortalized LβT2 gonadotrope cell line and rat primary cell cultures. In contrast, the saturated palmitate was ineffective. ACTH or TSH secretion was unaffected by UFA treatment. We demonstrated in LβT2 cells that linoleate effect is mediated neither by activation of membrane fatty acid (FA) receptors GPR40 or GPR120 although we characterized these receptors in LβT2 cells, nor through nuclear peroxisome proliferator-activated receptors. Furthermore, linoleate β-oxidation is not required for its action on LH secretion. In contrast, pharmacological inhibition of protein kinase C (PKC) or ERK pathways significantly prevented linoleate-stimulated LH release. Accordingly, linoleate was shown to activate novel PKC isoforms, PKCε and -θ, as well as ERK1/2 in LβT2 cells. Lastly, unsaturated, but not saturated, FA inhibited GnRH-induced LH secretion in LβT2 cells as well as in pituitary cell cultures. Altogether, these results suggest that the pituitary is a relevant site of FA action and that UFA may influence reproduction by directly interfering with basal and GnRH-dependent gonadotrope activity.