O conhecimento de diversos aspectos da Neuroanatomia de primatas não humanos - que atualmente é falho, pela falta de trabalhos a respeito - é importante não apenas pela importância intrínseca desse conhecimento como até pelo fato de contribuir para um melhor entendimento da própria evolução do grupo, o que representa um fator relevante para a sua preservação e proteção. O objetivo deste trabalho é efetuar estudos morfológicos da hipófise do macaco Cebus apella a fim de conhecer melhor esta estrutura, e oferecer subsídios para análises comparativas mais amplas. Utilizamos 11 animais sendo 7 deles constantes do acervo de pesquisa da Universidade Federal de Uberlândia e, os outros 4 exemplares, doados pelo IBAMA-MG. A preparação das peças anatômicas foi levada a efeito mediante cuidadosa dissecção dos espécimes, cujos encéfalos foram retirados das caixas cranianas, preservando-se ao máximo todas as suas estruturas. As hipófises, depois de registrada sua macroscopia, foram submetidas aos métodos histológicos de rotina para observações em microscopia de luz e eletrônica de transmissão. Dos resultados obtidos podemos citar que a hipófise, neste animal, é uma glândula intracraniana alojada na sela turcica, fixada à base do cérebro pelo infundíbulo, sendo este muito curto. Ela exibe forma odontóide, exibindo-se aparentemente, como uma massa única, pois macroscopicamente apenas é possível, a identificação de uma divisão discreta em um lobo anterior e outro posterior, além do infundíbulo. As análises histológicas mostram esta glândula dividida em três lobos: anterior (adenohipófise), intermédio e posterior (neurohipófise). À microscopia eletrônica de transmissão foi possível identificar e classificar 4 tipos celulares em relação á adenohipófise: células do tipo I, II, III e IV. O aspecto do núcleo dessas células, exibindo freqüentemente, invaginações profundas de sua membrana, confere à hipófise do macaco Cebus apella, características peculiares, o que nos instiga a realizar novas pesquisas sobre o assunto / The knowledge of many aspects of Neuroanatomy of non-human primates - which is currently poor due to the lack of studies on the subject - is very important not only for the intrinsic significance of the knowledge itself but also because it contributes for a better understanding of the evolution of the group, which represents a relevant factor for its preservation and protection. The objective of this study is to perform morphological researches on the hypophysis of the Cebus apella monkey in order to understand this structure better and to provide basis for wider comparative analyses. Eleven animals were used on this study. Seven of them were properties of the research collection of the Federal University of Uberlândia and the other four were donated by the IBAMA-MG. The preparation of the anatomical parts was carefully done through dissection of the specimens, whose encephalus were removed from their skulls preserving all their structures. The hypophysis, after having their macroscopy registered, were submitted to histological methods of routine for observation in light microscopy and electronic microscopy of transmission. We could conclude from the obtained results that the hypophysis, on this particular animal, is a intracranial gland lodged in the sela turcica fixed to the base of the brain by the infundibulum which is very short. It has in dens shape and it presents itself as a single mass, because, macroscopically, it is only possible the identification of a discrete division in an anterior lobe and another posterior one besides the infundibulum. The histological analyses show this gland divided in three lobes: anterior (adenohypophysis), intermediary and posterior (neurohypophysis). Through the electronic microscopy of transmission it was possible to identify and classify four cellular types related to the adenohypophysis: types I, II, III and IV. The aspect of the cores of these cells, frequently showing deep invaginations of their membranes, confers to hypophysis of the Cebus apella monkey, peculiar characteristics, which instigates us to carry on performing new studies on the subject

No description available.

Mammotropes were successfully identified in the anterior pituitary gland of Miniopterus schreibersii using immunocytochemical (ICC) staining at the light and electron microscopy level. Mammotropes were distributed throughout the gland, were polygonal in shape and during secretory activity contained numerous large secretory granules (350 - 800nm). Using double ICC labelling, prolactin and growth hormone were never co-localiszed and found in individual cells only. Plasma prolactin levels were successfully measured on a monthly basis using radioimmunoassay and monthly pituitary prolactin levels were quantified using morphometric analysis of immunogold ICC staining and densitometry with polyacrylamide gels. Seasonal changes in the ultrastructure of mammotropes, and pituitary and plasma prolactin concentrations in female Miniopterus schreibersii indicated that there was an increase in prolactin secretion during the second half of the period of delayed implantation and that prolactin secretion remained elevated during normal embryonic development and lactation. This suggests that prolactin may be part of the luteotropic and lactogenic complex, and that the hormone might be responsible for terminating the period of delayed implantation. The latter is supported by experiments, where exogenous prolactin initiated precocious implantation during early delayed implantation, and treatment with bromocryptine (which inhibits prolactin synthesis) retarded implantation. Activation of mammotropes to synthesise prolactin and an increase of plasma prolactin levels occurred shortly after the winter solstice (21 June), suggesting that increasing daylength may be the environmental cue, which terminates the period of delayed implantation in Miniopterus schreibersii.

The postnatal period is a critical time for development where external influences can help shape the long-term structure and function of the brain. Adverse experiences or stressors during the postnatal period, such as abuse or neglect, can have huge consequences on the long term function, health and susceptibility to disease. One environmental factor, whose importance is becoming increasingly more recognised for normal development, is light. Abnormal light during the first three weeks of life has been shown to have long term effects on the circadian system of rodents. On the other hand, the effects of abnormal light during the postnatal period on the stress system have yet been relatively unexplored. Therefore the aim of this thesis was to assess if altered postnatal light environment, such as that a preterm baby might be exposed to, has any long-term effects on the stress system. Mice were raised under constant light (LL), constant darkness (DD) or a normal 12:12hr light:dark cycle (LD) for the first three weeks of life from postnatal day (P)1 up until P21. From P21, all mice were then housed in LD conditions and the stress system was assessed by looking at several different levels of the HPA axis including neuropeptide expression in the brain, body and adrenal weight, and plasma corticosterone levels under both basal and stressed conditions. Learning and memory, anxiety-like behaviour and circadian output rhythms were also evaluated. Finally, mother-pup behaviour and maternal HPA axis were assessed to see if maternal care was changed by altered postnatal light. Both LL and DD rearing caused changes in the HPA axis of offspring with LL raised mice showing alterations in neuropeptide and glucocorticoid receptor expression in the brain. Postnatal DD resulted in a blunted corticosterone response to a stressor in females but had no effect in males. In terms of behaviour, LL raised mice had increased depressive-like behaviour. In contrast, postnatal light appears to have no effect on learning and memory or anxiety behaviour. When we looked at circadian output rhythms, we found that LL rearing appears to confer resilience to the rhythm disrupting effects of LL later on in life as seen by the maintenance of locomotor activity, body temperature and plasma corticosterone rhythms in LL. Maternal care and maternal stress systems appeared unaltered under the different postnatal light environments suggesting that the changes we see in the offspring are attributed to mechanisms other than alterations in maternal care.

Die Entwicklung der Hypophyse ist ein komplexer Prozess, an dem viele Transkriptionsfaktoren beteiligt sind. Bedeutende Funktionen haben die Bone Morphogenetic Proteins 2, 4 und 7. Ziel der Arbeit war es, an Patienten mit angeborener kombinierter Hypophyseninsuffizienz diese 3 Gene auf Mutationen zu untersuchen. Dabei wurden die Exons, Exon-Intron-Übergänge sowie die 3`- und 5`-untranslatierten Regionen sequenziert. Neu identifizierte Varianten wurden anschließend in einer gesunden Kontrollkohorte untersucht, um pathogenetisch nicht relevante Genvarianten auszuschließen. Um die funktionelle Relevanz der Varianten beurteilen zu können, wurden phylogenetische Analysen und Untersuchungen mittels Programmen zum Einfluss auf die Proteinstruktur und -funktion durchgeführt. Neben bekannten Varianten, konnten wir neue Varianten mit und ohne Aminosäureaustausch identifizieren. Eine neue Mutation im kodierenden Bereich von BMP4 erschien dabei besonders relevant. Wir konnten sie nur bei einem Patienten nachweisen, der zusätzlich zur kombinierten Hypophyseninsuffizienz Skelettveränderungen aufwies. Die hohe Konservierung und diese spezifische Klinik legen eine funktionelle Relevanz nahe.

Introduction Acromegaly is an endocrine disorder characterized by excessive growth hormone production.The most common cause is a benign pituitary adenoma, which can be an isolated tumor or part of a group of concomitant endocrine neoplasms. We present a case of a middle aged woman with sleep apnea and a newly diagnosed acromegaly secondary to a pituitary macroadenoma. Case presentation A 51-year-old woman was seen in the endocrinology clinic for evaluation of hyperparathyroidism and mild hypercalcemia. She had no symptoms related to hypercalcemia. However, she complained of enlargement of her fingers and toes. She also reported galactorrhea and breast engorgement. There was no hyperhidrosis or frontal bossing present and she denied headaches or vision symptoms. Past medical history was significant for obstructive sleep apnea. Insulin like growth factor level was 630 ng/ml (reference 53 - 190 ng/ml), prolactin level was 109 ng/ml (reference 1.9- 25 ng/ml), and Follicular stimulating hormone was 0.4mIU/ml (reference 1.2 - 21.0 mIU/ml). TSH, free T4, ACTH, and cortisol were normal. The labs were consistent with pituitary macroadenoma secreting growth hormone (GH) and prolactin. MRI pituitary showed a 1.9 cm macroadenoma with no evidence of optic nerve compression. Due to the coexisting diagnoses of hyperparathyroidism and pituitary adenoma, CT abdomen was done to evaluate for neuroendocrine tumor and to rule out Multiple Endocrine Neoplasia (MEN) Type 1. She then underwent transsphenoidal resection of the pituitary, with immunostaining reflecting diffuse prolactin and patchy GH expression. Post-surgery IGF, prolactin, thyroid function tests were normal. She was started on hydrocortisone replacement due to abnormal ACTH and cortisol. Her calcium levels normalized, and further genetic testing for MEN was abandoned. Her repeat sleep study also showed resolution of sleep apnea. She did not suffer from further symptoms of acromegaly and was scheduled for periodic surveillance for thyroid axis dysfunction. Discussion Dysregulated growth hormone production seen in acromegaly leads to increased GH and IGF-1 levels. It has many ramifications including debilitating arthritis from osteoarthropathy, glucose intolerance due to insulin resistance, higher propensity for GI neoplasms, and macroglossia with prognathism causing sleep apnea. Average lifespan is decreased by 30% due to cardiovascular and pulmonary dysfunction. Treatment is aimed at decreasing IGF levels and controlling any mass effect or metabolic abnormalities caused by the tumor. Treatment options include invasive procedures for good surgical candidates and medical therapy via somatostatin analogue for patients who are not. Residual or unresectable tumors can be treated with medical therapy or radiation therapy if there is no response to medication.

Muscarinic ligand binding sites in fragments of rat hypothalamus and pituitary were studied using [3H]quinuclidinyl benzilate (QNB). In the hypothalamus, the highest amount of specific QNB binding was to n. paraventricularis and n. dorsomedialis. Specific QNB binding in other hypothalamic regions varied within a relatively narrow range. Fragments of whole pituitary also bound QNB but to a much smaller degree than brain. Pituitary binding of QNB was blocked by atropine but not by hexamethonium or d-tubocurarine. Within the pituitary, specific QNB binding to posterior pituitary was three times greater than to anterior pituitary. These findings are consistent with the operation of cholinergic mechanisms in hypothalamic and pituitary function.

In this study, the structure and function of gonadotropin-releasing hormone (GnRH) in different vertebrate species, in the classes Aves, Reptilia and Pisces was investigated. Acetic acid extracts were subjected to gel filtration chromatography and semipreparative high performance liquid chromatography (HPLC) to partially purify the GnRHs. The GnRH immunoreactivity was then characterized by analytical HPLC, and by assaying HPLC fractions by radioimmunoassay with region-specific antisera generated against mammalian GnRH, Gln⁸-GnRH and Trp⁷,Leu⁸-GnRH and assessing luteinizing hormone (LH)-releasing activity of fractions in a chicken dispersed anterior pituitary cell bioassay. Five GnRH molecular forms have thusfar been structurally characterized in vertebrate brain. In mammals a GnRH with the structure pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂ has been demonstrated in the hypothalamus (Matsuo et al., 1971; Burgus et al., 1972). Gln⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH were present in chicken hypothalamus (King and Millar, 1982a, 1982c; Miyamoto et al., 1983, 1984), Trp⁷,Leu⁸-GnRH in salmon brain (Sherwood et al., 1983) and Tyr³,Leu⁵,Glu⁶,Trp⁷,Lys⁸-GnRH in lamprey brain (Sherwood et al., 1986). In ostrich (Struthio camelus) hypothalamus two GnRHs with identical properties to Gln⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH have been demonstrated, as well as four other LR-releasing factors with different chromatographic and immunological properties to any of the known naturally-occurring GnRHs. Since Gln⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH were also present in chicken hypothalamus it appears likely that these two GnRHs occur in all birds. In alligator (Alligator mississippiensis) brain only two GnRHs were detected. These forms co-eluted with Gln⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH in two HPLC systems. They cross-reacted similarly to the two synthetic peptides with antisera directed against mammalian GnRH and Gln⁸-GnRH and released LH from chicken dispersed anterior pituitary cells in a similar manner to the synthetic peptides. The Archosaurs (alligators and crocodiles) are believed to be closely related to birds and therefore it seems likely that they should have identical GnRHs. In skink (Calcides ocellatus tiligugu) brain one GnRH, which co-eluted with His⁵,Trp⁷,Tyr⁸-GnRH, was demonstrated. Two other lizards (Cordylis nigra and Pordarcis s. sicula) have been studied (Powell et al., 1985; R.C. Powell, G. Ciarcia, V. Lance, R.P. Millar and J.A. King, submitted). In c. nigra four immunoreactive GnRHs were detected, two of which co-eluted released chicken LH similarly to, Trp⁷,Leu⁸-GnRH and with, and His⁵,Trp⁷,Tyr⁸-GnRH. In P. s. sicula a GnRH molecular form similar to Trp⁷,Leu⁸-GnRH occurred as well as two novel GnRHs. It thus appears that Gln⁸-GnRH does not occur in lower reptiles, but His⁵,Trp⁷,Tyr⁸-GnRH and/or Trp⁷,Leu⁸-GnRH do. His⁵,Trp⁷,Tyr⁸-GnRH appears to he a widespread GnRH, occurring in vertebrates as diverse as birds and elasmobranch fish. In dogfish (Poroderma africanum) brain seven factors, which stimulated release of LH from chicken dispersed anterior pituitary cells, were separated on analytical HPLC. Two of these factors were partially characterized as Trp⁷,Leu⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH. Three of the other forms cross-reacted with GnRH antisera, but appear to be novel GnRHs. In teleost (Coris julis) brain two GnRHs similar to Trp⁷,Leu⁸-GnRH and His⁵,Trp⁷,Tyr⁸-GnRH were present. These two GnRHs therefore appear to occur in both fish species studied. Trp⁷,Leu⁸-GnRH is widespread amongst teleost fish (Jackson and Pan, 1983; Sherwood et al., 1983; Breton et al., 1984; Sherwood et al., 1984; King and Millar, 1985). From these data it seems evident that the mammalian GnRH molecular form occurs only in mammals and amphibians, Gln⁸-GnRH in birds and higher reptiles, and Trp⁷,Leu⁸-GnRH in gnathostomes. His⁵,Trp⁷, Tyr⁸-GnRH appears to he present in numerous different vertebrates. Tyr³,Leu⁵,Glu⁶,Trp⁷,Lys⁸-GnRH has thus far only been detected in lamprey brain. A number of novel GnRHs, whose structures have not been elucidated are present.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24488号 / 医博第4930号 / 新制||医||1063(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 渡邉 大, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM