The prepartum surge in fetal plasma cortisol, essential for the maturation of organs in mammals and the normal timing of parturition in some species, including sheep, may result from an increase in the molar ratio of adrenocorticotropin (ACTH) to pro-opiomelanocortin (POMC) in the fetal circulation. Related to this, the cleavage of POMC to ACTH by the enzyme, prohormone convertase 1 (PC1), may be influenced by corticotrophin releasing hormone (CRH) stimulation. Accumulating evidence suggests that the capacity of individual corticotrophs to process POMC to ACTH may vary and individual corticotrophs are differentially responsive to CRH. It is not known, however, if there are separate corticotroph subpopulations in the fetal sheep pituitary which can be identified by differential colocalisation of POMC, ACTH and the CRH receptor 1, CRHR₁, nor if changes in the relative proportions of such subpopulations play a role in the molecular mechanisms underlying the overall changes in pituitary function described previously during gestation and in response to suboptimal uterine environments. To investigate these hypotheses, it was first necessary to develop novel methods for the simultaneous immunohistochemical labelling of POMC, ACTH and CRHR₁ in individual cells on sections of fetal sheep pituitary. In addition, I developed and validated an automated method to categorise and count individual cells to increase the quantitative power of this study. Pituitary tissue was collected from control fetuses at 53-55 (n=6), 63-85 (n=6), 110 (n=4), 139-141 (n=4) and 144-145 (n=6) days gestation. Two animal models, known to alter pituitary function in the fetal sheep, were used to investigate corticotrophic adaptations to suboptimal uterine environments. For the maternal periconceptional undernutrition (PCUN) model, maternal feed was reduced to 70% of maintenance requirements from at least 45 days before to 7 days after mating and fetal tissues were collected at 53-55 days gestation (n=7). For the placental restriction (PR) model, the majority of the placental attachment sites were removed in five ewes before mating and fetal tissues were collected at 140 (n=4) and 144 (n=4) days gestation. Pituitary sections were simultaneously labelled with antisera raised against full length POMC, ACTH and CRHR₁ and the proportions of pituitary cells with combinations of antisera were quantified. Four subpopulations of corticotrophs were identified, which expressed either: POMC+ACTH+CRHR₁, ACTH+CRHR₁, POMC+ CRHR₁ or POMConly. There was a significant decrease in the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ between 53-55 and 65-85 days gestation, before an increase at 110 days gestation and a further marked decrease between 139-141 and 144-145 days gestation. In fetuses from the PCUN group, the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ in early gestation was reduced. PR resulted in a significantly higher proportion of corticotrophs expressing POMC+ACTH+CRHR₁ during the prepartum period. This work represents the discovery of the differential expression of POMC, ACTH and CRHR₁ in individual corticotrophs of the fetal sheep pituitary and the first insights into the pituitary adaptations to periconceptional nutrient restriction and placental restriction at the level of individual corticotrophs. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1337370 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

To identify known genes or expressed sequence tags (ESTs) which are expressed specifically or preferentially in the chicken hypothalamus and pituitary gland related to highly reproductive performance, two reciprocal cDNA libraries were constructed using a subtractive hybridization strategy. Two different strains, L2 (dam line; n=12) and B (sire line; n=12) of Taiwan Country Chickens (TCCs), which were originated from one single strain and further subjected to 40-wk egg production and comb size, body weight, respectively since 1982, were used in our study. A total of 324 and 370 clones were identified from L2-subtract-B and B-subtract-L2 hypothalamus/pituitary cDNA libraries. 311 and 360 single inserted sequences from each cDNA library, 53 and 23 non-redundant candidate genes were identified. Quantitative reverse-transcription (RT)-PCR were used to validate the association of mRNA expression profiles of the identified candidate genes and high-egg yield trait in another 118 hypothalamuses and pituitary glands that were dissected from seven different chicken stocks, including B-, L2-, Black-, Red-feather TCCs, commercial Single-Comb White Leghorn (WL) layer at National Chung-Hsing University (NCHU) and Red-feather TCCs grouped into high eggs (Red-high) & low eggs (Red-low) to 40 wks of age at National Chiayi University (NCYU). Among identified genes including known genes and novel genes, involving 33 screened genes, Inhibitor-1 of protein phosphatase type 2A (ANP32A), 3-hydroxybutyrate dehydrogenase (BDH), Contactin (CNTN1), Deiodinase iodothyronine type II (DIO2), Inhibitor of growth family, member 3 (ING3), Lysosomal-associated transmembrane protein 4 beta (LAPTM4B), Neural cell adhesion molecule 1 (NCAM1), DJ-1 protein (PARK7), Prostaglandin D2 synthase (PGDS), Prolactin (PRL), Protocadherin 1 (PCDH1), Pleiomorphic adenoma gene 1 (PLAG1), GTP-binding protein SAR1a (SAR1A), Secretogranin II (SCG2), Stathmin 2 (STMN2), T-box protein 2 (TBX2) were up-regulated in B-subtract-L2 cDNA library. Among above-mentioned 16 identified genes, there were 9 genes related to high-egg yield in chickens., including BDH, NCAM1, PCDH1, PGDS, PLAG1, PRL, SAR1A, SCG2, STMN2.

Der GLI2-Transkriptionsfaktor ist eines der Haupt Effektor-Proteine des Sonic Hedgehog (SHH)-Signalweges und hat vermutlich eine Schlüsselfunktion in der Entwicklung der Hypophyse. Genomische GLI2-Veränderungen welche zu abgeschnittenen Proteinen führten, wurden beschrieben als Ursache für Holoprosenzephalie (HPE) oder HPE-ähnliche Veränderungen, teilweise in Verbindung mit einer Hypophysenunterfunktion. Ziel dieser Arbeit war die Ermittlung der Frequenz von GLI2-Mutationen in Patienten mit multiplem hypophysärem Hormonausfall (multiple pituitary hormone deficiency, MPHD) und eine funktionelle Untersuchung der gefunden Mutationen mittels Transkriptionsaktivitäts-Untersuchungen durch funktionelle Luciferase assays. Hierfür wählten wir Teilnehmer der GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study)-Studie. Patienten bei denen bereits Mutationen eines der etablierten Gene für MPHD nachgewiesen wurde, wurden ausgeschlossen. Insgesamt haben wir 168 Patienten mit MPHD untersucht. Bei allen Patienten waren mindestens ein GH- und ein TSH-Mangel dokumentiert, Auffälligkeiten in der zentralen Bildgebung mittels cMRT wurden bei 96 Patienten angegeben. In fünf Studienteilnehmern wurden vier verschiedene heterozygote missense Varianten nachgewiesen, hiervon wurden zwei bislang noch nicht in der Literatur beschrieben. Eine Variante, pR516P, führte in den in-vitro Experimenten zu einem kompletten Verlust der Proteinaktivität. Zusätzlich zu einem Wachstumshormonmangel hatte der Träger dieser Mutation einen Mangel an TSH und der Gonadotropine, sowie einen nichtdeszendierten Hypophysenhinterlappen und eine Polydaktylie, aber keine ersichtlichen Mittelliniendefekte. Anhand der funktionellen Untersuchung konnten wir erstmalig nachweisen, dass ein heterozygoter Aminosäuren-Austausch im GLI2-Protein zu einer möglichen Funktionseinschränkung der Transkriptionsaktivität führen kann und somit die Ursache für MPHD mit milden extrahypophysären Auffälligkeiten sein könnte. Der Phänotyp von GLI2-Mutationen ist variabel und die Penetranz ist unvollständig. GLI2-Mutationen sind assoziiert mit einer Hypoplasie des Hypophysenvorderlappens und treten gehäuft mit einem ektopen Hypophysenhinterlappen auf.

There are a number of links between the endocrine system and the nervous system. In this study, the impact of ischemic stroke on the endocrine system was investigated. Elderly volunteers were studied because data regarding the influence of advanced age on endocrine parameters were lacking. Only small differences in pituitary-thyroid and pituitary-adrenal hormone axes were found between two groups of elderly patients, 60 and 80 years of age. The 80-year-old age group had a lower thyrotropin response to thyrotropin releasing hormone (TRH) and a decline in dopamine excretion. Patients with acute ischemic stroke showed a pronounced hypercortisolism studied by the dexamethasone test and urine free cortisol measurements. In multiple regression analyses, postdexamethasone cortisol levels were positively correlated to proximity of the lesion to the frontal pole of the brain and disorientation. Urine cortisol levels were predicted by limb paresis, disorientation and body temperature. High cortisol excretion was associated with a worse functional outcome. Norepinephrine excretion was correlated to urine cortisol levels and to motor impairment. Patients with acute stroke had elevated free thyroxin indices. A paradoxical growth hormone response to TRH was found in the majority of stroke patients. In a multiple regression model disorientation was negatively correlated to thyrotropin response after TRH and positively correlated to prolactin response. Growth hormone response to TRH was associated with extensive paresis. In a cohort study diabetic and non-diabetic patients were prospectively studied after an initial stroke. Diabetes mellitus adversely influenced survival, the risk for a recurrent stroke and myocardial infarction. / <p>S. 1-66: sammanfattning, s. 69-190: 6 uppsatser</p> / digitalisering@umu

The prepartum surge in fetal plasma cortisol, essential for the maturation of organs in mammals and the normal timing of parturition in some species, including sheep, may result from an increase in the molar ratio of adrenocorticotropin (ACTH) to pro-opiomelanocortin (POMC) in the fetal circulation. Related to this, the cleavage of POMC to ACTH by the enzyme, prohormone convertase 1 (PC1), may be influenced by corticotrophin releasing hormone (CRH) stimulation. Accumulating evidence suggests that the capacity of individual corticotrophs to process POMC to ACTH may vary and individual corticotrophs are differentially responsive to CRH. It is not known, however, if there are separate corticotroph subpopulations in the fetal sheep pituitary which can be identified by differential colocalisation of POMC, ACTH and the CRH receptor 1, CRHR₁, nor if changes in the relative proportions of such subpopulations play a role in the molecular mechanisms underlying the overall changes in pituitary function described previously during gestation and in response to suboptimal uterine environments. To investigate these hypotheses, it was first necessary to develop novel methods for the simultaneous immunohistochemical labelling of POMC, ACTH and CRHR₁ in individual cells on sections of fetal sheep pituitary. In addition, I developed and validated an automated method to categorise and count individual cells to increase the quantitative power of this study. Pituitary tissue was collected from control fetuses at 53-55 (n=6), 63-85 (n=6), 110 (n=4), 139-141 (n=4) and 144-145 (n=6) days gestation. Two animal models, known to alter pituitary function in the fetal sheep, were used to investigate corticotrophic adaptations to suboptimal uterine environments. For the maternal periconceptional undernutrition (PCUN) model, maternal feed was reduced to 70% of maintenance requirements from at least 45 days before to 7 days after mating and fetal tissues were collected at 53-55 days gestation (n=7). For the placental restriction (PR) model, the majority of the placental attachment sites were removed in five ewes before mating and fetal tissues were collected at 140 (n=4) and 144 (n=4) days gestation. Pituitary sections were simultaneously labelled with antisera raised against full length POMC, ACTH and CRHR₁ and the proportions of pituitary cells with combinations of antisera were quantified. Four subpopulations of corticotrophs were identified, which expressed either: POMC+ACTH+CRHR₁, ACTH+CRHR₁, POMC+ CRHR₁ or POMConly. There was a significant decrease in the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ between 53-55 and 65-85 days gestation, before an increase at 110 days gestation and a further marked decrease between 139-141 and 144-145 days gestation. In fetuses from the PCUN group, the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ in early gestation was reduced. PR resulted in a significantly higher proportion of corticotrophs expressing POMC+ACTH+CRHR₁ during the prepartum period. This work represents the discovery of the differential expression of POMC, ACTH and CRHR₁ in individual corticotrophs of the fetal sheep pituitary and the first insights into the pituitary adaptations to periconceptional nutrient restriction and placental restriction at the level of individual corticotrophs. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1337370 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

The prepartum surge in fetal plasma cortisol, essential for the maturation of organs in mammals and the normal timing of parturition in some species, including sheep, may result from an increase in the molar ratio of adrenocorticotropin (ACTH) to pro-opiomelanocortin (POMC) in the fetal circulation. Related to this, the cleavage of POMC to ACTH by the enzyme, prohormone convertase 1 (PC1), may be influenced by corticotrophin releasing hormone (CRH) stimulation. Accumulating evidence suggests that the capacity of individual corticotrophs to process POMC to ACTH may vary and individual corticotrophs are differentially responsive to CRH. It is not known, however, if there are separate corticotroph subpopulations in the fetal sheep pituitary which can be identified by differential colocalisation of POMC, ACTH and the CRH receptor 1, CRHR₁, nor if changes in the relative proportions of such subpopulations play a role in the molecular mechanisms underlying the overall changes in pituitary function described previously during gestation and in response to suboptimal uterine environments. To investigate these hypotheses, it was first necessary to develop novel methods for the simultaneous immunohistochemical labelling of POMC, ACTH and CRHR₁ in individual cells on sections of fetal sheep pituitary. In addition, I developed and validated an automated method to categorise and count individual cells to increase the quantitative power of this study. Pituitary tissue was collected from control fetuses at 53-55 (n=6), 63-85 (n=6), 110 (n=4), 139-141 (n=4) and 144-145 (n=6) days gestation. Two animal models, known to alter pituitary function in the fetal sheep, were used to investigate corticotrophic adaptations to suboptimal uterine environments. For the maternal periconceptional undernutrition (PCUN) model, maternal feed was reduced to 70% of maintenance requirements from at least 45 days before to 7 days after mating and fetal tissues were collected at 53-55 days gestation (n=7). For the placental restriction (PR) model, the majority of the placental attachment sites were removed in five ewes before mating and fetal tissues were collected at 140 (n=4) and 144 (n=4) days gestation. Pituitary sections were simultaneously labelled with antisera raised against full length POMC, ACTH and CRHR₁ and the proportions of pituitary cells with combinations of antisera were quantified. Four subpopulations of corticotrophs were identified, which expressed either: POMC+ACTH+CRHR₁, ACTH+CRHR₁, POMC+ CRHR₁ or POMConly. There was a significant decrease in the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ between 53-55 and 65-85 days gestation, before an increase at 110 days gestation and a further marked decrease between 139-141 and 144-145 days gestation. In fetuses from the PCUN group, the proportion of pituitary cells expressing POMC+ACTH+CRHR₁ in early gestation was reduced. PR resulted in a significantly higher proportion of corticotrophs expressing POMC+ACTH+CRHR₁ during the prepartum period. This work represents the discovery of the differential expression of POMC, ACTH and CRHR₁ in individual corticotrophs of the fetal sheep pituitary and the first insights into the pituitary adaptations to periconceptional nutrient restriction and placental restriction at the level of individual corticotrophs. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1337370 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

Made available in DSpace on 2015-07-22T20:49:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-31. Added 1 bitstream(s) on 2015-08-11T03:25:33Z : No. of bitstreams: 1 Publico-0144.pdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A cirurgia dos tumores selares é tradicionalmente um campo de atuação dos neurocirurgiões. Contudo, desde a retomada da abordagem transeptaltransesfenoidal para acessar a sela túrcica, na década de sessenta do século passado, os otorrinolaringologistas têm exercido importante parceria neste procedimento. A divulgação da cirurgia endoscópica nasossinusal na otorrinolaringologia criou o interesse pela sua aplicação na cirurgia da região selar. a uso do endoscópio permitiu acesso transnasal direto ao seio esfenoidal sem a necessidade de descolamento do septo nasal, com menor desconforto para o paciente, além de morbidade pós-operatória inferior aos métodos tradicionais. Objetivo: O objetivo deste trabalho foi verificar as dificuldades técnicas, intercorrências e complicações pós-operatórias, no manejo otorrinolaringológico do acesso transnasal endoscópico à sela túrcica. Método: Foram analisados retrospectivamente os prontuários e imagens de arquivo de 159 pacientes submetidos à cirurgia da região selar entre março de 2001 e dezembro de 2005, na Universidade Federal de São Paulo / Escola Paulista de Medicina. Foram incluídos neste estudo 91 pacientes submetidos a um total de 95 procedimentos por via transnasal endoscópica. Resultados: Foi possível a realização da técnica endoscópica transnasal em todos os pacientes estudados, independente de idade, presença de variações anatômicas, características e etiologia do tumor, e antecedente de cirurgia prévia. Não houve necessidade de remoção da concha média ou correção de desvios septais para realização do procedimento cirúrgico em nenhum dos casos. A principal intercorrência foi a abertura do diafragma selar durante a remoção de tumores, causando fístula liquórica intra-operatória em 13,68 por cento dos casos. As complicações pós-operatórias encontradas foram: sangramento nasal (8,42 por cento), fístula liquórica (8,42 por cento), e meningite (2,19 por cento). Conclusão: O acesso endoscópico transnasal aos tumores selares pôde ser realizado de forma minimamente invasiva, preservando-se as estruturas nasais nos 95 procedimentos estudados, independente da idade do paciente, características e etiologia do tumor. / Sellar tumor surgery is traditionally a neurosurgeon´s field. However, since the renewed interest in the transseptal-transsphenoidal approach to access the sellar region in the sixties, otolarynngologists have played an important partnership in this procedure. Divulging of endoscopic sinus surgery in otolaryngology created an interest in its application in sellar region surgery. The use of endoscopes allowed a direct transnasal approach to the sphenoidal sinus without need of dissection of the septal mucosa, with less post-operative discomfort and morbidity inferior to that of traditional methods. Objective: The objective of this work was to verify the technical difficulties, intercurrences and post-operative complications in the otolaryngological handling of the endoscopic transnasal approach to the sellar region. Method: The analisys comprised both the files and archive images of 159 patients submitted to sellar region surgery between march 2001 and December 2005, at Universidade Federal de São Paulo / Escola Paulista de Medicina. 91 patients submitted to a total of 95 endoscopic transnasal procedures were included in this study. Results: It was possible to apply the endoscopic transnasal tecnique in all studied patients, independent of age, anatomical variations, tumor characteristics and etyology, and previous surgery history. There was no need of middle turbinate removal, or septal deviations corrections for the surgical procedure in any of the cases. The main intercurrence was the opening of the sellar diaphragm during the removal of the the tumors, causing intra-operative CSF leak in 13.68% of the cases. The post-operative complications encountered were: nasal bleeding (8.42%), CSF leak (8,42%), and meningitis (2.19%). Conclusion: Transnasal endoscopic approach to sellar tumors was done in a minimally invasive form, preserving the nasal structures in the 95 studied procedures, independently of patient age, tumor characteristics and etyology. / TEDE / BV UNIFESP: Teses e dissertações

Neste estudo foi verificado que a hipófise de S. brasiliensis era composta por dois tecidos, a neuro hipófise (NH) e a adeno-hipófise (AH). Nesta última, foram distinguidos sete tipos celulares. Na RPD foram detectadas as células adrenocorticotrópicas e prolactínicas, na PPD as células gonadotrópicas, somatotrópicas e tireotrópicas, e na PI, as células melanotrópicas e somatolactínicas. Foi evidenciada única célula gonadotrópica, produtora de LH e FSH. O primórdio da hipófise foi detectado 12 horas após a eclosão (hpe), a NH com 72 hpe e o início da formação do pedúnculo com 300 hpe. Nos juvenis (600 hpe), a hipófise apresentou uma morfologia semelhante àquela observada nos adultos. As células prolactínicas foram detectadas com 12 hpe, juntamente com as células adrenocorticotrópicas e melanotrópicas, seguidas das somatotrópicas e somatolactínicas, com 36 hpe. Por outro lado, nas larvas e juvenis foram detectadas duas populações distintas de células gonadotrópicas, as células produtoras de FSH foram detectadas com 600 hpe, enquanto as produtoras de LH com 120 hpe. / This study showed that the pituitary gland of S. brasiliensis was formed by two tissues, neurohypophysis and adenohypophysis. In the latter, seven cell types were distinguished. In RPD, prolactin and adrenocorticotropic cells were present. In PPD, gonadotropic, somatotrope and thyrotropic cells were detected, and in PI, somatolactin and melanotropic cells were found. Interestingly, was detected a single gonadotropic cell responsible for producing both gonadotropins. The primordium of the pituitary gland was detected 12 hours after hatching (hah), the neurohypophysis was detected 72 hah and formation of the stalk 300 hah. In juveniles, 600 hah, the pituitary showed a similar morphology to that observed in adults of this species. Prolactin cells were detected 12 hah together with adrenocorticotropic and melanotropic cells, followed by somatotropic and somatolactin cells 36 hah. Unlike adults, larvae and juveniles have shown two distinct populations of gonadotropic cells. FSH-producing cells were detected 600 hah, while LH-producing cells were detected 120 hah.

En dépit de l'abondance de données scientifiques, les mécanismes cellulaires régulant la sécrétion du pic pré-ovulatoire de LH lors du proestrus, restent encore mal compris.Afin de pouvoir étudier les mécanismes sous-jacents à cette sécrétion, j’ai tout d’abord adapté des techniques innovantes d’imagerie fonctionnelle en microscopie de fluorescence in vivo, d’injections de vecteurs viraux dans l’hypophyse, d’optogénétique sur animal éveillé et d’immunohistofluorescence sur organe entier.J’ai ensuite montré la plasticité structurelle des cellules gonadotropes et des péricytes (cellules « murales » péri-vasculaires) lors du proestrus sur des hypophyses transparisées. Ce remodelage a permis de proposer l’existence d’une unité Gonadotrope-Vasculaire (GVU) composée des cellules gonadotropes, des capillaires fenêtrés et des péricytes dans laquelle ces derniers moduleraient le pic pré-ovulatoire de LH.La contraction des péricytes via l’activation de la Channelrhodopsine-2 a permis de mettre en évidence leur rôle dans la potentialisation de la sécrétion de LH chez des animaux libres de leurs mouvements et implantés d’une fibre optique.Des expériences de microscopie à l’aide d’une lentille GRIN implantée au-dessus de l’hypophyse ont permis, chez l’animal éveillé en configuration « tête-fixée », d’étudier le flux sanguin et l’activité calcique de cellules de la GVU exprimant GCaMP6. Cette étude a également été menée sur la face ventrale de l’hypophyse sur souris anesthésiée. Les résultats montrent une activité calcique in vivo augmentée dans les cellules endocrines hypophysaires et diminuée dans les péricytes lors d’une sécrétion de la LH induite par la GnRH. / In spite of abundance of scientific data, cellular mechanisms regulating the secretion of the pre-ovulatory LH surge during proestrus are still poorly understood.In order to study the mechanisms underlying this secretion, I adapted innovative tech-niques for in vivo fluorescence functional imaging, injection of viral vectors in the pitui-tary gland, optogenetics in awake animals and immunohistofluorescence in the whole organ.I then showed structural plasticity of gonadotroph cells and pericytes (perivascular "mural" cells) during proestrus in cleared hypophyses. This suggested the existence of a Gonadotroph-Vascular Unit (GVU) composed of gonadotroph cells, fenestrated capil-laries and pericytes, in which the latter would modulate the pre-ovulatory LH surge.Pericytes contraction via Channelrhodopsine-2 activation permitted to demonstrate their role in the sensitization of LH secretion in freely moving animals implanted with an optical fiber.Finally, blood flow and calcium activity in GVU cells expressing GCaMP6 were performed in awake « head-fixed » animals in which visualization of the pituitary gland was achievable through an implanted GRIN lens. These experiments were also conduct-ed at the ventral side of the pituitary gland in anesthetized mice. Analysis showed that in vivo calcium activity increases in endocrine cells and decreases in pericytes during GnRH-induced LH secretion.

Gonadotropin-releasing hormone (GnRH) and its superactive analogues are currently being used in the treatment of a number of endocrine disorders, such as endometriosis, precocious puberty, infertility and prostatic cancer. Selection of these analogues for clinical use have been previously based on their activities in animal models. This thesis has therefore investigated the binding characteristics of the human GnRH receptor, in comparison to those of the rat receptor, as well as the activities of a number of GnRH analogues for stimulating luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion from cultured human pituitary cells. The establishment of a human pituitary bioassay system has further made possible the investigation of the direct regulatory roles of GnRH and other neuropeptides in man. To date, such studies in man have been performed in vivo and are thus complicated by the simultaneous interactions of numerous modulators.