Neuroanatomical organization of the brain gonadotropin-inhibitory hormone and gonadotropin-releasing hormone systems in the frog Pelophylax esculentus.

Growing evidence suggests that gonadotropin-inhibitory hormone (GnIH) may play a key role in mediating vertebrate reproduction. GnIH inhibits gonadotropin synthesis and release by decreasing the activity of gonadotropin-releasing hormone (GnRH) neurons as well as by directly regulating gonadotropin secretion from the pituitary. Whereas the presence of GnIH has been widely investigated in various classes of vertebrates, there are very few immunohistochemical reports focusing on GnIH in amphibians. The aim of this study was to assess the presence and neuroanatomical distribution of GnIH-like immunoreactivity in the brain of the anuran amphibian Pelophylax (Rana) esculentus (esculenta) and to explore any potential anatomical relationship with mammalian GnRH-immunoreactive (mGnRH-ir) elements. The GnIH-like immunoreactive (GnIH-ir) system constitutes two distinct subpopulations in the telencephalon and diencephalon, with the highest number of immunoreactive cells located in the preoptic and suprachiasmatic areas. GnIH-ir neurons were also observed in the medial septum, the anterior commissure, the dorsal hypothalamus, the periventricular nucleus of the hypothalamus, and the posterior tuberculum. Scattered GnIH-ir fibers were present in all major subdivisions of the brain but only occasionally in the median eminence. mGnRH-ir neurons were distributed in the mediobasal telencephalon, the medial septal area, and the anterior preoptic area. Double-label immunohistochemistry revealed that the GnRH and GnIH systems coexist and have overlapping distributions at the level of the anterior preoptic area. Some GnIH-ir fibers were in close proximity to mGnRH-ir cell bodies. Our results suggest that both the neuroanatomy and the functional regulation of GnRH release are conserved properties of the hypothalamic GnIH-ir system among vertebrate species.

[Hypogonadotropic hypogonadism: new aspects in the regulation of hypothalamic-pituitary-gonadal axis]. / Hypogonadisme hypogonadotrope : notions récentes sur la régulation de l'axe hypothalamo-hypophyso-gonadique.

Hypogonadotropic hypogonadism (HH) is defined by the absence of sex steroid synthesis associated with the lack of appropriate gonadotrophin secretion. This leads to a variable degree of impuberism, often diagnosed during childhood or adolescence. Genetics of HH involve many genes. However, molecular defects have been identified in only 30 % of patients. Kallmann syndrome (KS) is defined by the association of HH and anosmia. Six genes are involved in KS (KAL1, FGFR1, FGF8, PROK2, PROKR2 and CHD7). However, genetics of KS is complex, because of the variability of the phenotype for a similar molecular defect. Otherwise, heterozygous anomalies are frequently described. Identification in the same patient of several mutations in some of these genes (digenism) could account for this variability. Autosomal recessive transmission is frequently observed in familial cases of HH without anosmia. Molecular alterations have been identified for several neuropeptides or their corresponding receptors, which are involved in the physiology of the gonadotropic axis : GNRHR, KISS1R/GPR54, neurokinin B (TAC3), TACR3 and GNRH1 (and PROK2, PROKR2 and CHD7). Anomalies of leptin or its receptor are also involved in HH cases. A new negative regulating element has been recently identified in humans : RFRP3, which is ortholog of the avian GnIH (gonadotrophin inhibitory hormone). Recent progress about these neuropeptides leads to a new model of comprehension of the gonadotropic axis physiology, from a linear model to a network model, which regulates the central element of regulation of the gonadotropic axis, represented by the GnRH neurons.

Seasonal effects of pimozide and des Gly10 [D-Ala6] LH-RH ethylamide on gonadotrophin secretion in goldfish.

The seasonal changes in the gonadotrophin-release-inhibitory activity of dopamine and responsiveness to gonadotrophin-releasing hormone were investigated by determining the effects of injection of pimozide, a dopamine receptor antagonist, des-Gly10 [D-Ala6] LH-RH ethylamide (LRH-A), or the combination of pimozide plus LRH-A on serum gonadotrophin (GtH) levels of goldfish, held at 12 or 20 degrees C, at different stages of gonadal development. As in previous studies, pimozide greatly potentiated the GtH-release response to LRH-A. The highest concentrations of serum GtH induced by injection of pimozide or LRH-A alone, or the combination of pimozide plus LRH-A were in females in late stages of ovarian recrudescence; fish that were sexually regressed (males and females combined) were the least responsive, and fish that were in early stages of gonadal recrudescence, and mature females ( = prespawning, completed ovarian recrudescence) were intermediate. Fish held at 20 degrees C had a more rapid onset of GtH release and had higher serum GtH levels initially compared to fish at 12 degrees C at similar sexual stages; however, the fish held at 12 degrees C generally had a more prolonged increase in serum GtH levels, indicating that temperature influence the time course of the GtH-release response. The results indicate that there is a seasonal variation in responsiveness to injection of pimozide, LRH-A and the combination of pimozide plus LRH-A. These seasonal changes may be due to differences in the pituitary content of GtH, the ability of the pituitary to synthesize GtH, or changes in GtH cell receptors for GnRH and dopamine, or a combination of these and other unknown factors.

Localization of hypophysiotropic neurohormones by assay of sections from various brain areas.

The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area.

The amenorrhoea-galactorrhea syndrome: present diagnostic and therapeutic perspectives. / La sindrome amenorrea-galatorrea: prospettive diagnostiche e terapeutiche attuali

Recent progress in the field of radioimmunology, especially as regards prolactin (PRL) assay, as well as the use of new drugs have opened new perspectives for a better understanding of the "amenorrhoea-galactorrhea syndrome" both from the diagnostic and therapeutic points of view. This syndrome which formerly was considered infrequent, is now observed more and more often, perhaps as a result of the more widespread use of drugs such as phenothiazines, reserpine derivatives, alpha-methyldopa and tricyclic antidepressants, as well as owing to the large-scale use of estrogens and above all of estrogen-progestogen contraceptives. The problems of etiopathogenesis and management of the amenorrhea-galactorrhea syndrome are complicated by the fact that a variety of factors are responsible, as is shown also by the classical nosographic classification with the Forbes-Albright syndrome in the presence of a pituitary tumour, the Chiari-Frommel syndrome of amenorrhea-galactorrhea following pregnancy, and the Argonz-del Castillo-Ahumada syndrome in the absence of lither pregnancy or tumor.