Problématique. Basée sur les constats effectués lors d’un essai clinique randomisé qui visait à évaluer les effets du lait maternel de fin d’expression sur la croissance et le développement de nouveau-nés prématurés et qui s’est soldé par un recrutement infructueux, une intervention de soutien à la lactation chez les mères de nouveau-nés prématurés a été développée. La mère d’un nouveau-né prématuré est en effet trois fois plus à risque qu’une autre de présenter une production lactée insuffisante. Il est donc crucial de soutenir ces mères dans l’établissement et le maintien d’une production lactée adéquate. Le but de cette étude pilote est d’estimer les effets d’une intervention de soutien à la lactation sur l’expression de lait maternel et la production lactée de mères ayant donné naissance prématurément ainsi que d’évaluer les aspects d’acceptabilité et de faisabilité de l’intervention, de l’étude et de ses procédures. Hypothèse de recherche. Les mères de nouveau-nés prématurés qui reçoivent une intervention de soutien à la lactation expriment leur lait significativement plus longtemps et plus fréquemment et produisent significativement un plus grand volume de lait à plus grande concentration lipidique sur une base quotidienne que celles qui reçoivent les soins usuels. Méthode. Devis : Projet-pilote de type essai clinique randomisé. Échantillon: Quarante mères de nouveau-nés prématurés de <30 semaines de gestation admis à une unité de soins intensifs néonatals. Procédures: Les mères du groupe témoin reçoivent les soins usuels alors que celles du groupe expérimental reçoivent une intervention de soutien à la lactation. Cette dernière comporte quatre volets: une séance d’enseignement portant sur l’établissement et le maintien d’une production lactée suffisante, un suivi téléphonique, une ligne d’aide téléphonique et le prêt d’un tire-lait électrique double pompage. Dans les deux groupes, les mères sont amenées à tenir un journal de bord de leurs séances d’expression et du volume de lait maternel exprimé. Résultats. L’étude et ses procédures de même que l’intervention de soutien sont acceptables et faisables. Les résultats observés en lien avec l’hypothèse de recherche sont orientés dans la même direction que cette dernière à l’exception de la concentration lipidique du lait maternel. Recommandations. Une étude à plus grande échelle doit être réalisée afin d’évaluer les effets de l’intervention de soutien à la lactation sur la production lactée de mères de nouveau-nés prématurés. Quant à la clinique, des actions concertées doivent être menées afin de créer un contexte propice et des conditions favorables à l’expression de lait maternel chez les mères de nouveau-nés prématurés. / Problem statement. Based on observations from an unsuccessful randomized clinical trial that aimed to evaluate the effects of hindmilk on the short-term growth and development of preterm infants, a lactation support intervention for mothers of preterm infants has been developed. Mothers who give birth prematurely are three times more likely to have an insufficient milk output compared to those who give birth at term. It is therefore crucial to support these mothers in order to facilitate the establishment and maintenance of their milk supply. The aim of this pilot study is to estimate the effects of a lactation support intervention on the expression of breast milk and milk output of mothers who gave birth prematurely and assess the acceptability and feasibility of the intervention, study and its procedures. Research hypothesis. A lactation support intervention in mothers who deliver prematurely enables them to express their milk significantly longer and more frequently, and produce a greater milk output with a higher lipid concentration compared to mothers who deliver prematurely and receive usual care. Method. Design: A pilot study of a randomized clinical trial. Sample: Forty mothers of preterm infants born at <30 weeks of gestation and admitted to a neonatal intensive care unit. Procedures: The mothers in the control group receive usual care while those in the experimental group receive a lactation support intervention. The intervention has four components: an education session on the establishment and maintenance of an adequate milk supply, a telephone follow-up, a telephone helpline and the loan of a double electric breast pump. In both the intervention and control groups, mothers kept a logbook of the frequency, duration and volume of their breast milk expressions. Results. Both the study design and the intervention are feasible and acceptable to mothers of preterm infants. With the exception of milk lipid concentration, the results are oriented in the same direction as the research hypothesis. Recommendations. A larger scale study should be conducted to evaluate the effects of the lactation support intervention on the frequency, duration, and volume of breast milk expression among mothers of premature infants. As for the clinical practice, concerted interprofessional actions must be undertaken to create the environment and conditions conducive to breast milk expression in these mothers.

The skeletal system is a dynamic organ that provides support, protection, aids in the production of all blood cells, and serves as a calcium ion reservoir. It is constantly undergoing a process called ‘remodeling’, which occurs through the actions of osteoclast and osteoblast cells. The former is responsible for breaking down bone whereas the latter secretes an organic matrix for bone synthesis. Two experiments were conducted to analyze the effects of physiological perturbations on the bone remodeling process. Specifically, the impact of aging and selective serotonin re-uptake inhibitor administration coupled with lactation on bone morphology and composition were observed. The bony skeleton is not a stagnant organ, rather it undergoes functional, mechanical, and compositional changes throughout life. Thus, we wanted to determine the consequences age had on various bone parameters and found a decrease in bone volume fraction (BV/TV), trabecular number (Tb.N), cortical thickness (C.Th), and an increase in periosteal area, endosteal area, and cortical porosity (C.Po). In regards to pregnancy, post-partum depression is a common condition. As a result, many women utilize selective serotonin re-uptake inhibitors (SSRIs) to combat the negative symptoms associated with it. Serotonin is an important hormone involved in mood regulation and the mammary-derived form has a role in lactation. It induces the production of parathyroid hormone-related protein, which is essential for regulating maternal calcium. Because the calcium source for milk production is derived from the maternal bone, we were interested in the impact peri-partum usage of SSRIs had on maternal bone mineral density. Additionally, we sought to understand the effect that circulating SSRIs had on the bone formation of pups. Analysis revealed age-related decreases in BV/TV, Tb.N, trabecular thickness (Tb.Th), C.Th and increases in trabecular spacing (Tb.Sp) and C.Po, with the effects being exacerbated in cohorts treated with a SSRI during lactation. We did not observe, however, any change in trabecular bone mineral density (Tb.BMD) or cortical bone mineral density (C.BMD) over time. In regards to the pups, we observed similar results to those of the dams in addition to a significant reduction in femur length. With the data obtained from the two projects, we hope that they bring awareness to potential consequences that physiological perturbations may have on the bone remodeling process. Both experiments have clinical correlations to humans. Further understanding the relationship between aging and bone may aid in developing methodologies to prevent age-related changes. On the other hand, analyzing the effects that SSRI usage has on maternal and child bone density may result in alternative methods to combat post-partum depression.

O cobalto é um dos principais componentes das ligas metálicas fundidas amplamente utilizadas na odontologia. Ele é considerado o constituinte de 45 a 70% de inúmeros trabalhos protéticos. Há evidência de elementos metálicos causarem toxicidade sistêmica e local. Este trabalho teve como objetivo, avaliar os efeitos do cobalto no epitélio juncional, epitélio adamantino, epitélio da gengiva inserida e ligamento periodontal do 1° molar superior do rato, durante a lactação. Para tal, foram utilizados ratos com 1 dia de vida pós-natal, cujas mães receberam 300mg de cloreto de cobalto por litro de água destilada no bebedouro (grupo tratado -T) e ratos cujas mães não receberam CoCl2 (grupo controle - C), durante toda a lactação. Ao final de 21dias, os filhotes foram sacrificados com sobredosagem anestésica. As cabeças foram separadas e fixadas em solução de alfac (álcool 80%- 85ml, formalina 10ml e ácido acético 5ml) incluídas em parafina e os cortes frontais seriados foram corados com hematoxilina e eosina. Os cortes foram focalizados ao microscópio de luz (100X), munido de uma câmara clara. Os núcleos das células dos tecidos estudados foram projetados sobre o papel com aumento final de 1000X e 50 núcleos de cada estrutura foram contornados com lápis preto para posterior medição do diâmetros maior (D) e menor (d). Uma vez determinados os diâmetros, foram estimados os seguintes parâmetros cariométricos: diâmetro geométrico médio, relação entre D/d, perímetro, área, volume, relação entre volume e área, excentricidade, coeficiente de forma e índice de contorno. Neste trabalho também foi utilizada uma grade impressa sobre papel. As imagens obtidas foram desenhadas sobre a grade. A grade pode ser usada tanto para contar pontos sobre uma determinada estrutura histológica bem como para contar intersecções entre duas estruturas contíguas, bastando para isso, no primeiro caso, considerar o número de pontos que caem sobre a estrutura em estudo, ou, no segundo caso, o número de vezes em que as superfícies vizinhas cortam a linha curva. Com a finalidade de se avaliar o volume citoplasmático, o volume celular, a relação núcleo/citoplasma, a densidade numérica celular, a relação superfície externa/camada basal, a espessura das camadas epiteliais e a densidade de superfície, foi utilizada ora a contagem de pontos ora o número de intersecções e aplicados às equações estereológicas apropriadas para cada uma dessas variáveis. Todos os dados colhidos foram submetidos à estatística não paramétrica - Teste de Wilcoxon-Mann-Whitney. Os núcleos dos tecidos estudados mostraram valores diminuídos, após cariometria, para os diâmetros maior, menor e médio; volume, área, perímetro e relação volume/área. Estereologicamente foi possível observar, no epitélio juncional, epitélio adamantino e no epitélio da gengiva inserida, células menos volumosas com citoplasma mais escasso levando a um maior número de células por mm3 de tecido. O ligamento periodontal também se apresentou desorganizado e com fibras de menor tamanho. Neste estudo, o cobalto ocasionou um quadro de hipotrofia epitelial, indicando uma ação direta nos epitélios juncional e adamantino, epitélio da gengiva inserida bem como no ligamento periodontal. / Cobalt is one of the main components of cast metal alloys broadly used in dentistry. It is the constituent of 45 to 70% of numerous prosthetic works. There is evidence that metal elements cause systemic and local toxicity. The purpose of the present study is to evaluate cobalt effects on the junctional epithelium, adamantine epithelium, inserted gum epithelium, and periodontal ligament of the superior first molar in rats, during lactation. To do this, 1-day old rats were used, whose mothers received 300mg of cobalt chloride per liter of distilled in the drinker (treated group T) and rats whose mothers did not receive CoCl2 (control group C), during lactation. After 21 days, the rat pups were killed with an anesthetic overdose. The heads were separated and fixed in an alfac solution (80% alcohol-85ml, formaline-10ml, and acetic acid-5ml), embedded in paraffin and stained with hematoxylin and eosin. The cuts were viewed under a light microscope (100X) with a clear chamber. The nucleus of the studied tissue cells were projected on paper with a final increase of 100X. Fifty nuclei from each structure were outlined with a black pencil so that the greater (D) and smaller (d) diameters could be measured. After determining the diameters, the following cariometric parameters were established: mean geometric diameter, D/d relation, perimeter, area, volume, volume/area relation, eccentricity, form coefficient, and contour index. This study also used a grid printed on paper. The images obtained were drawn over the grid, which was used to count points over a certain histological structure as well as to count intersections between two contiguous structures. All that was needed, in the first case, was to consider the number of points located over the studied structure, or, in the second case, the number of times that neighboring surfaces cut the curve line. With the aim to evaluate the cytoplasmic volume, cellular volume, cytoplasm/nucleus relation, cellular numeric density, external surface/basal layer relation, the thickness of epithelial layers, and surface density, point counting was used at times and, at others, the number of intersections was considered and applied to the appropriate stereological equations for each variable. All the collected data were subjected to non-parametric statistics Wilcoxon-Mann-Whitney Test. The nuclei of the studied tissues showed reduced values after cariometry for: greater, smaller, and mean diameter; volume; area; perimeter; and volume/area relation. Stereologically, it was observed, in the junctional epithelium, adamantine epithelium, and in the inserted gum epithelium, cells with less volume and with scarce cytoplasm, which caused a greater number of cells per mm3 of tissue. The periodontal ligament was also disorganized and with smaller fibers. In this study, cobalt caused epithelial hypertrophy symptoms, indicating a direct action on the junctional and adamantine epithelium, inserted gum epithelium, as well as on the periodontal ligament.

Há evidência de elementos metálicos causarem toxicidade sistêmica e local. Este trabalho teve como objetivo, avaliar os efeitos do zinco no epitélio adamantino, epitélio juncional, gengiva inserida e ligamento periodontal do 1° molar superior do rato, durante a lactação. Para tal, foram utilizados ratos com 1 dia de vida pós-natal, cujas mães receberam 300 mg de cloreto de zinco (ZnCl2) por litro de água destilada no bebedouro (grupo tratado - T) e ratos cujas mães não receberam o ZnCl2 (grupo controle - C), durante toda a lactação. Ao final de 21dias, os filhotes foram sacrificados com sobredosagem anestésica. As cabeças foram separadas e fixadas em solução de alfac (álcool 80% - 85ml; formalina - 10ml e ácido acético - 5ml) incluídas em parafina e os cortes frontais seriados foram corados com hematoxilina e eosina. Os cortes foram focalizados ao microscópio de luz (100X), munido de uma câmara clara. Os núcleos das células dos tecidos estudados foram projetados sobre o papel com aumento final de 1000X e 50 núcleos de cada estrutura foram contornados com lápis preto para posterior medição do diâmetros maior (D) e menor (d). Uma vez determinados os diâmetros, foram estimados os seguintes parâmetros cariométricos: diâmetro geométrico médio, relação D/d, perímetro, área, volume, relação entre volume e área, excentricidade, coeficiente de forma e índice de contorno. Neste trabalho também foi utilizada uma grade impressa sobre papel. As imagens obtidas foram desenhadas sobre a grade. A grade pode ser usada tanto para contar pontos sobre uma determinada estrutura histológica bem como para contar intersecções entre duas estruturas contíguas, bastando para isso, no primeiro caso, considerar o número de pontos que caem sobre a estrutura em estudo, ou, no segundo caso, o número de vezes em que as superfícies vizinhas cortam a linha curva. Com a finalidade de se avaliar o volume citoplasmático, o volume celular, a relação núcleo/citoplasma, a densidade numérica celular, a relação superfície externa/camada basal, a espessura das camadas epiteliais e a densidade de superfície, foram utilizadas ora a contagem de pontos, ora o número de intersecções e aplicados às equações estereológicas apropriadas para cada uma dessas variáveis. Todos os dados colhidos foram submetidos à estatística não paramétrica Teste de Wilcoxon - Mann - Whitney. Os núcleos dos tecidos estudados mostraram valores diminuídos, após cariometria, para os diâmetros maior, menor e médio; perímetro, área, volume e relação volume/área. Estereologicamente foi possível observar, no epitélio juncional, epitélio adamantino e no epitélio da gengiva inserida, células menos volumosas, levando a um maior número de células por mm3 de tecido. O ligamento periodontal também se apresentou desorganizado e com fibras de menor tamanho. Pode-se concluir que zinco trouxe alterações nos epitélios juncional e adamantino, gengiva inserida bem como no ligamento periodontal, após avaliações morfométricas e estereológicas. / There is evidence that metal elements cause systemic and local toxicity. The purpose of the present study is to evaluate zinc effects on the adamantine epithelium, junctional epithelium, inserted gum and periodontal ligament of the superior first molar of rat, during lactation. To do this, 1- day old rats were used, whose mothers received 300 mg of zinc chloride (ZnCl2) per liter of distilled in the drinker (treated group T) and rats whose mothers did not receive ZnCl2 (control group C), during lactation. After 21 days, the rat pups were killed with an anesthetic overdose. The heads were separated and fixed in an alfac solution (80% alcohol - 85ml, formaline - 10ml, and acetic acid - 5ml), embedded in paraffin and stained with hematoxylin and eosin. The cuts were viewed under a light microscope (100X) with a clear chamber. The nucleus of the studied tissue cells were projected on paper with a final increase of 1000X and fifty nuclei from each structure were outlined with a black pencil so that the greater (D) and smaller (d) diameters could be measured. After determining the diameters, the following cariometric parameters were established: mean geometric diameter, D/d relation, perimeter, area, volume, volume/area relation, eccentricity, form coefficient, and contour index. This study also used a grid printed on paper. The images obtained were drawn over the grid, which was used to count points over a certain histological structure as well as to count intersections between two contiguous structures. All that was needed, in the first case, was to consider the number of points located over the studied structure, or, in the second case, the number of times that neighboring surfaces cut the curve line. With the aim to evaluate the cytoplasmic volume, cellular volume, cytoplasm/nucleus relation, cellular numeric density, external surface/basal layer relation, the thickness of epithelial layers, and surface density, point counting was used at times and, at others, the number of intersections was considered and applied to the appropriate stereological equations for each variable. All the collected data were subjected to non - parametric statistics Wilcoxon - Mann - Whitney Test. The nuclei of the studied tissues showed reduced values after cariometry for: greater, smaller, and mean diameter; perimeter, area, volume and volume/area relation. Stereologically, it was observed, in the junctional epithelium, adamantine epithelium, and in the inserted gum epithelium, cells with less volume, which caused a greater number of cells per mm3 of tissue. The periodontal ligament was also disorganized and with smaller fibers. It was possible to conclude that zinc caused alterations in the adamantine epithelium, junctional epithelium, inserted gum and periodontal ligament, after morphometric and stereological evaluations.

Office Care of Women covers a wide range of topics which are pertinent to the provision of excellent healthcare. Common gynecologic topics are discussed in depth, as well as non-gynecologic medical conditions which are frequently faced by female patients. This book is designed as a single source reference which covers the majority of topics seen by clinicians as they care for women patients in the office setting. The fifty chapters include topics unique to female patients but also include other health conditions which are affected by the patient's gender. The authors of this book span six specialties and three continents thereby giving the reader a comprehensive source of information to improve the healthcare of women.

The objective of this study was to examine the potential effects of supplementing excess crystalline tryptophan (trp) in the lactation diets of sows. Sixty-one sows of varying parity were fed either a control diet (0.26% trp) or a treatment diet with an extra two grams of tryptophan (0.30% trp). Over the 28 day lactation period utilized by the production site, sow and litter performance were recorded. Sow performance was measured by backfat loss, blood urea nitrogen, milk composition, return to estrus, wean to estrus interval, and conception rate. Litter performance was measured as average weaning weight, number weaned, and pre-wean mortality. The control and treatment groups were further subdivided by parity for statistical analysis. Sows of parity one and two were classified as primiparous, while sows of parity three or more were classified as multiparous. There were no significant differences (P≤0.05) between the control and treatment diets even with regards to parity groups. There was one trend (0.05 0.10) in which treatment multiparous sows had higher litter weaning weight (P=0.055) than the control multiparous sows. In summary, these results indicate that increasing the tryptophan level in this lactation diet by two grams did not significantly influence sow or litter performance.

Abstract not available

The decline in fertility in dairy cows is of international concern. Since 1950, milk production demands have increased while first service rates of conception have decreased. It is unclear why fertility has decreased, however current dairy management practice requires cows to be kept on a tight yearly calving schedule to ensure maximum milk production over the lifetime of the cow. The current postulate suggests that this regime places a high metabolic burden on the cows, which in turn requires the breakdown of tissues such as fat and muscle to provide substrates to meet the increased energy demands of lactation. Immediately after calving, dairy cows enter a state of negative energy balance (EB), as they cannot consume enough energy to sustain lactation. During this period of negative EB, fat is mobilised in the form of non-esterified fatty acids to help supply the body with the extra energy it needs, but fat mobilisation decreases after four weeks while cows remain in a state of negative EB for several more weeks. It is unclear whether or not muscle breakdown occurs and plays a role in the restoration of EB in lactating cows during peak lactation. I hypothesized that the breakdown of muscle does occur in cows during peak lactation, and that it occurs to a greater extent in cows producing higher amounts of milk. Dairy cows from three strains, NZL, NZH and OSH, representing cows with differing milk production abilities (low, intermediate and high, respectively), were studied for 12 weeks postpartum. Blood was drawn at weekly intervals and muscle biopsies taken at -1, 1, 4, 8, and 12 weeks postpartum. Analysis of plasma revealed an increase in the abundance of troponin I-fs (a marker of muscle breakdown) over the period of study, suggesting that breakdown of skeletal muscle was occurring. Real-time polymerase chain reaction analysis showed that expression of the ubiquitin-proteasome (UbP) ligases atrogin-1 (atro1) and muscle ring finger protein 1 (murf1) increased initially, but returned to normal levels by four weeks postpartum. Concentration of mRNA of the lysosomal proteases, cathepsin B, D, H and L, did not change over the period of study. Therefore, the UbP pathway may contribute to the breakdown of muscle detected by troponin I-fs in plasma. Proteins involved in translation initiation were examined by Western blotting. The ratio of phosphorylated over total eIF2alpha and 4E-BP1 remained unchanged throughout the study, indicating that the breakdown of muscle was not a result of decreased protein synthesis. However, there was a greater ratio of phosphorylated to total eIF2alpha in NZL cows compared with NZH and OSH, suggesting that protein synthesis was less overall in NZL cows than other strains. Measurement of myosin heavy chain composition indicated there was no change in the abundance of type I and type IIx muscle fibres and plasma myostatin levels did not change over the period of study. However, the OSH cows had less myostatin in their plasma than the NZL and NZH cows, suggesting that there may be inhibition of muscle growth occurring in this strain. The results of this study suggest that breakdown of muscle could be important in restoring the EB in high-producing dairy cows during peak lactation. Upregulation of the UbP pathway during the first four weeks of lactation may contribute to this muscle breakdown. However, it remains unclear what processes then continue to regulate breakdown of skeletal muscle to maintain the elevated abundance of troponin I-fs in plasma from four to 12 weeks postpartum in lactating dairy cows.

Under normal circumstances, prolactin regulates its own release via a short-loop negative feedback mechanism in which prolactin, secreted from lactotrophs situated within the anterior pituitary gland, stimulates dopaminergic neurons in the hypothalamus to release dopamine into portal blood circulation. Dopamine, in turn, inhibits lactotroph activity. A change in this regulation of prolactin secretion is seen during late pregnancy where tuberoinfundibular dopaminergic (TIDA) neurons no longer respond to elevated levels of placental lactogen (PL), a lactogen structurally and functionally similar to prolactin, allowing a prolonged elevation of prolactin secretion and the induction of an antepartum prolactin surge (Andrews et al., 2001). The mechanisms behind this loss of responsiveness have not yet been determined. Prolactin acts by binding to its receptor on TIDA neurons and activating the signal transducer and activator of transcription 5b (STAT5b). During lactation, prolactin-induced activation of STAT5b is suppressed. This reduction in STAT5b signalling is consistent with a loss in TIDA responsiveness and is correlated with an increase in suppressor of cytokine signalling (SOCS) messenger ribonucleic acid (mRNA) expression within the arcuate nucleus. As SOCS proteins are known to disrupt prolactin signalling by interfering with STAT signalling in other systems, it is likely that the change in TIDA responsiveness to prolactin or PL during late pregnancy occurs at least partially in response to an increase in SOCS proteins at this time. Although prolactin can induce SOCS mRNA expression within the arcuate nucleus, the level of SOCS mRNA expression observed on day 20 of pregnancy is significantly lower to that observed on day 22. As PL is elevated on day 20 of pregnancy, some other factor or a combination of factors unique to the final 2 days of pregnancy induces the change in prolactin signalling. Late pregnancy is associated with elevated levels of estrogen while progesterone significantly declines. The aim of this study was to test the hypothesis that a fall in progesterone in the presence of elevated levels of estrogen during late pregnancy induces the increase in SOCS levels within TIDA neurons. This then results in a disruption of prolactin signalling, a decline in dopamine production and release, and the induction of the antepartum prolactin surge. To determine if ovarian steroid hormones can act directly on TIDA neurons during late pregnancy, expression of progesterone receptors (PR) and estrogen receptors (ER) within TIDA neurons were examined during pregnancy and lactation. Using double-labelled immunohistochemistry, expression of both steroid receptors within arcuate dopaminergic neurons during pregnancy and lactation was confirmed. This is consistent with the hypothesis that changing levels of steroid hormones might directly regulate TIDA activity. Furthermore, as the level of steroid receptor expression within TIDA neurons did not change significantly during pregnancy and lactation, it is likely that changing levels of serum estrogen and progesterone may affect these neurons at this time. To investigate the potential effects of steroid hormones on prolactin-induced and non prolactin-induced expression of SOCS mRNA, ovariectomised rats were treated with bromocriptine to suppress endogenous prolactin, and were then treated with a regime of chronic progesterone and/or estrogen in the presence and absence of an induced prolactin surge. SOCS mRNA expression within the arcuate nucleus was measured using real time quantitative RT-PCR. It was found that both estrogen and prolactin independently induced SOCS mRNA expression within the arcuate nucleus, but high levels of progesterone inhibited this effect. This supported the hypothesis that a change in SOCS mRNA expression within TIDA neurons might occur following the changes in steroid hormone levels observed during late pregnancy. To specifically investigate the role of estrogen and progesterone in regulating SOCS expression during late pregnancy, an animal model was designed to experimentally alter estrogen and progesterone levels during late pregnancy, and then SOCS mRNA expression was examined. In this model, advancing the late pregnant decline in progesterone resulted in a significant advance in the timing of the antepartum prolactin surge and parturition, while delaying the decline in progesterone abolished the antepartum prolactin surge and delayed parturition. Furthermore, within this model, elevated levels of SOCS mRNA expression were always observed following the withdrawal of progesterone. This suggested that following the decline in progesterone during late pregnancy, elevated levels of estrogen (or PL) are able to induce SOCS mRNA expression within the arcuate nucleus. Given that SOCS proteins disrupt cytokine signalling in other systems, the induction of SOCS proteins during late pregnancy would then presumably mediate the change in TIDA responsiveness to prolactin. To determine whether it was possible to change prolactin responses without affecting parturition, it was hoped to specifically alter progesterone and estrogen signalling in the brain. This was done by centrally administering progesterone to maintain progesterone levels during late pregnancy, and the ER antagonist ICI-182,780 (ICI) to block central estrogen levels. To determine the effectiveness of intracerebroventricular (icv) administration of ICI, two central estrogen mediated endpoints were evaluated: estrogen negative feedback on gonadotrophin releasing hormone (GnRH) pulse frequency (as measured by the frequency luteinizing hormone (LH) pulses) and the induction of PR within hypothalamic nuclei. Also, to confirm that central administration of ICI did not have a peripheral effect, estrogen induced uterine proliferation was measured. Although central ICI administration at the maximum possible dose affected estrogen-induced GnRH pulse frequency and partially reduced estrogen-induced PR expression within arcuate dopaminergic neurons, ICI did not affect the antepartum prolactin surge. Furthermore, cental administration of progesterone did not abolish the antepartum prolactin surge. This suggested that central administration of ICI and progesterone as a tool for researching central actions of ovarian steroids is likely to be limited to certain central endpoints, and was not suitable as a model to study central steroid effects on prolactin regulation. Overall, the progression of the findings in this study led to the formulation of a key hypothesis: that during late pregnancy, elevated levels of estrogen and the withdrawal of progesterone allows for the prolactin-induced increase of SOCS proteins within TIDA neurons. Elevated levels of SOCS proteins may then disrupt normal prolactin signalling, mediated via the JAK/STAT pathway. This results in reduced dopamine synthesis and release and, the subsequent induction of the antepartum prolactin surge.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Public Health." Includes bibliographical references (p. 97-102).