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001-es BibID:	BIBFORM041509
Első szerző:	Hrabovszky Erik
Cím:	Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept / Hrabovszky E., Sipos M. T., Molnár C. S., Ciofi P., Borsay B. Á., Gergely P., Herczeg L., Bloom S. R., Ghatei M. A., Dhillo W. S., Liposits Z.
Dátum:	2012
ISSN:	0013-7227
Megjegyzések:	Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated in the generation of GnRH neurosecretory pulses and in the negative feedback effects of sexual steroids to the reproductive axis. To test the validity and limitations of the KNDy neuron concept in the human, we carried out the comparative immunohistochemical analysis of the three neuropeptides in the infundibular nucleus (Inf; also known as arcuate nucleus) and stalk of young male human individuals (<37 yr). Results of quantitative immunohistochemical experiments established that the regional densities of NKB immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, were about 5 times as high as those of the KP-IR elements. Dual-immunofluorescent studies confirmed that considerable subsets of the NKB-IR and KP-IR cell bodies and fibers are separate, and only about 33% of NKB-IR perikarya and 75% of KP-IR perikarya were dual labeled. Furthermore, very few DYN-IR cell bodies could be visualized in the Inf. DYN-IR fibers were also rare and, with few exceptions, distinct from the KP-IR fibers. The abundance and colocalization patterns of the three immunoreactivities showed similar trends in the infundibular stalk around portal blood vessels. Together these results indicate that most NKB neurons in the Inf do not synthesize detectable amounts of KP and DYN in young male human individuals. These data call for a critical use of the KNDy neuron terminology when referring to the putative pulse generator system of the mediobasal hypothalamus. We conclude that the functional importance of these three neuropeptides in reproductive regulation considerably varies among species, between sexes, and at different ages.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Endocrinology. - 153 : 10 (2012), p. 4978-4989. -
További szerzők:	Sipos Máté T. Molnár Csilla S. (Budapest) Ciofi, Philippe Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Gergely Péter (1974-) (igazságügyi orvosszakértő) Herczeg László (1954-) (igazságügyi orvosszakértő) Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Liposits Zsolt
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001-es BibID:	BIBFORM041252
035-os BibID:	PMID:22654828
Első szerző:	Hrabovszky Erik
Cím:	Sexual dimorphism of kisspeptin and neurokinin B immunoreactive neurons in the infundibular nucleus of aged men and women / Erik Hrabovszky, Csilla S. Molnár, Máté T. Sipos, Barbara Vida, Philippe Ciofi, Beáta A. Borsay, László Sarkadi, László Herczeg, Stephen R. Bloom, Mohammad A. Ghatei, Waljit S. Dhillo, Imre Kalló, Zsolt Liposits
Dátum:	2011
Megjegyzések:	The secretory output of gonadotropin-releasing hormone (GnRH) neurons is critically influenced by peptidergic neurons synthesizing kisspeptins (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus (Inf). These cells mediate negative feedback effects of sex steroids on the reproductive axis. While negative feedback is lost in postmenopausal women, it is partly preserved by the sustained testosterone secretion in aged men. We hypothesized that the different reproductive physiology of aged men and women is reflected in morphological differences of KP and NKB neurons. This sexual dimorphism was studied with immunohistochemistry in hypothalamic sections of aged human male (?50?years) and female (>55?years) subjects. KP and NKB cell bodies of the Inf were larger in females. The number of KP cell bodies, the density of KP fibers, and the incidence of their contacts on GnRH neurons were much higher in aged women compared with men. The number of NKB cell bodies was only slightly higher in women and there was no sexual dimorphism in the regional density of NKB fibers and the incidence of their appositions onto GnRH cells. The incidences of NKB cell bodies, fibers, and appositions onto GnRH neurons exceeded several-fold those of KP-IR elements in men. More NKB than KP inputs to GnRH cells were also present in women. Immunofluorescent studies identified only partial overlap between KP and NKB axons. KP and NKB were colocalized in higher percentages of afferents to GnRH neurons in women compared with men. Most of these sex differences might be explained with the lack of estrogen negative feedback in aged women, whereas testosterone can continue to suppress KP, and to a lesser extent, NKB synthesis in men. Overall, sex differences in reproductive physiology of aged humans were reflected in the dramatic sexual dimorphism of the KP system, with significantly higher incidences of KP-IR neurons, fibers and inputs to GnRH neurons in aged females vs. males.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Frontiers in endocrinology [electronic resource]. - 2 (2011), p. 80. -
További szerzők:	Molnár Csilla S. (Budapest) Sipos Máté T. Vida Barbara Ciofi, Philippe Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Sarkadi László Herczeg László (1954-) (igazságügyi orvosszakértő) Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Kalló Imre Liposits Zsolt
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001-es BibID:	BIBFORM041254
035-os BibID:	PMID:22510271
Első szerző:	Hrabovszky Erik
Cím:	Glutamatergic and GABAergic innervation of human gonadotropin-releasing hormone-I neurons / Erik Hrabovszky, Csilla S. Molnár, Robert Nagy, Barbara Vida, Beáta Á. Borsay, Kálmán Rácz, László Herczeg, Masahiko Watanabe, Imre Kalló, Zsolt Liposits
Dátum:	2012
ISSN:	0013-7227
Megjegyzések:	Amino acid (aa) neurotransmitters in synaptic afferents to hypothalamic GnRH-I neurons are critically involved in the neuroendocrine control of reproduction. Although in rodents the major aa neurotransmitter in these afferents is ?-aminobutyric acid (GABA), glutamatergic axons also innervate GnRH neurons directly. Our aim with the present study was to address the relative contribution of GABAergic and glutamatergic axons to the afferent control of human GnRH neurons. Formalin-fixed hypothalamic samples were obtained from adult male individuals (n = 8) at autopsies, and their coronal sections processed for dual-label immunohistochemical studies. GABAergic axons were labeled with vesicular inhibitory aa transporter antibodies, whereas glutamatergic axons were detected with antisera against the major vesicular glutamate transporter (VGLUT) isoforms, VGLUT1 and VGLUT2. The relative incidences of GABAergic and glutamatergic axonal appositions to GnRH-immunoreactive neurons were compared quantitatively in two regions, the infundibular and paraventricular nuclei. Results showed that GABAergic axons established the most frequently encountered type of axo-somatic apposition. Glutamatergic contacts occurred in significantly lower numbers, with similar contributions by their VGLUT1 and VGLUT2 subclasses. The innervation pattern was different on GnRH dendrites where the combined incidence of glutamatergic (VGLUT1 + VGLUT2) contacts slightly exceeded that of the GABAergic appositions. We conclude that GABA represents the major aa neurotransmitter in axo-somatic afferents to human GnRH neurons, whereas glutamatergic inputs occur somewhat more frequently than GABAergic inputs on GnRH dendrites. Unlike in rats, the GnRH system of the human receives innervation from the VGLUT1, in addition to the VGLUT2, subclass of glutamatergic neurons.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Endocrinology. - 153 : 6 (2012), p. 2766-2776. -
További szerzők:	Molnár Csilla S. (Budapest) Nagy Róbert (Budapest) Vida Barbara Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Rácz Kálmán (1981-) (igazságügyi rezidens) Watanabe, Masahiko Kalló Imre Liposits Zsolt Herczeg László (1954-) (igazságügyi orvosszakértő)
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001-es BibID:	BIBFORM041511
Első szerző:	Molnár Csilla S. (Budapest)
Cím:	Morphological evidence for enhanced kisspeptin and neurokinin B signaling in the infundibular nucleus of the aging man / Molnár C. S., Vida B., Sipos M. T., Ciofi P., Borsay B. Á., Rácz K., Herczeg L., Bloom S. R., Ghatei M. A., Dhillo W. S., Liposits Z., Hrabovszky E.
Dátum:	2012
ISSN:	0013-7227
Megjegyzések:	Peptidergic neurons synthesizing kisspeptin (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus have been implicated in negative sex steroid feedback to GnRH neurons. In laboratory rodents, testosterone decreases KP and NKB expression in this region. In the present study, we addressed the hypothesis that the weakening of this inhibitory testosterone feedback in elderly men coincides with enhanced KP and NKB signaling in the infundibular nucleus. This central hypothesis was tested in a series of immunohistochemical studies on hypothalamic sections of male human individuals that were divided into arbitrary "young" (21-49 yr, n = 11) and "aged" (50-67 yr, n = 9) groups. Quantitative immunohistochemical experiments established that the regional densities of NKB-immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, exceeded several times those of the KP-IR elements. Robust aging-dependent enhancements were identified in the regional densities of KP-IR perikarya and fibers and the incidence of afferent contacts they established onto GnRH neurons. The abundance of NKB-IR perikarya, fibers, and axonal appositions to GnRH neurons also increased with age, albeit to lower extents. In dual-immunofluorescent studies, the incidence of KP-IR NKB perikarya increased from 36% in young to 68% in aged men. Collectively, these immunohistochemical data suggest an aging-related robust enhancement in central KP signaling and a moderate enhancement in central NKB signaling. These changes are compatible with a reduced testosterone negative feedback to KP and NKB neurons. The heavier KP and NKB inputs to GnRH neurons in aged, compared with young, men may play a role in the enhanced central stimulation of the reproductive axis. It requires clarification to what extent the enhanced KP and NKB signaling upstream from GnRH neurons is an adaptive response to hypogonadism or, alternatively, a consequence of a decline in the androgen sensitivity of KP and NKB neurons.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Endocrinology. - 153 : 11 (2012), p. 5428-5439. -
További szerzők:	Vida Barbara Sipos Máté T. Ciofi, Philippe Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Rácz Kálmán (1981-) (igazságügyi rezidens) Herczeg László (1954-) (igazságügyi orvosszakértő) Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Liposits Zsolt Hrabovszky Erik
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