Maternal Pituitary Gland Research Articles

Pituitary Hypertrophy

Pituitary adenomas are the most common cause of sellar masses although there are a number of other neoplastic, infectious, inflammatory, developmental, and vascular etiologies that should be considered. Pregnancy promotes a physiological increase in the size of the maternal pituitary gland, especially adenohypophysis. The normal maturation sequence of the pituitary gland apparently involves a period of physiological hypertrophy in teenagers. As most incidentalomas in pediatric patients are not associated with hormonal hypersecretion or hypopituitarism, and structural progression is not common, it is hypothesized that the extensive follow-up assessment recommended for adults might not be necessary for children. Patients presenting with a pituitary lesion should undergo a complete history and physical examination that includes evaluations for evidence of hypopituitarism and hormone hypersecretion syndrome. Patients with evidence for either of these conditions should undergo an appropriately directed biochemical evaluation. All patients presenting with a pituitary lesion abutting the optic nerves or chiasm on magnetic resonance imaging should undergo a formal visual field examination. Emergencies in pituitary disease can result from the failure of the pituitary gland to secrete one or more pituitary hormones or from neuro-ophthalmological symptoms due to the mass effect of an expanding hypothalamic-pituitary lesion. Early diagnosis and prompt treatment of endocrine emergencies are mandatory.

MON-346 A Rare Case of Recurring Adrenal Hemorrhage with Consecutive Pregnancies

Introduction - Adrenal hemorrhage (AH) during pregnancy is a rare condition with an incidence ranging from 0.14% to 1.1%. The objective of this report is to describe a case of recurring AH in successive pregnancies. Case Report - A 25-year-old female, G3P1011, 33 weeks of gestation, presented to the ER with the chief complaint of left flank pain. Her past medical history was pertinent for spontaneous abortion of first pregnancy, spontaneous right AH and adrenal insufficiency during the second pregnancy, with an eventual spontaneous vaginal delivery of viable child following medical management. History was negative for personal or family history of thromboembolic disease, anticoagulation use, trauma, signs or symptoms of infection. On admission, her vitals were stable. Pertinent physical exam findings were tenderness to deep palpation of the abdomen on the left upper quadrant. Laboratory results, including hemoglobin, were within normal limits. The US of abdomen revealed fat stranding surrounding the left adrenal gland. Given the concern for AH, after discussing risks and benefits, a CT abdomen without IV contrast was done and revealed abnormally enlarged left adrenal gland with high density, suggestive of hemorrhage. Her random serum cortisol level was low (0.7μg/dL; 7-28 μg/dL). Basal, 30-minute, and 60-minute serum cortisol with low dose ACTH stimulation testing were 0.6μg/dL (minimum 5.5μg/dL), 2.0μg/dL (minimum 7μg/dL), 3.1μg/dL (minimum 18μg/dL), confirming primary adrenal insufficiency and she was started on IV hydrocortisone. Work up for hypercoagulability and bleeding disorder comprising ANA, anticardiolipin antibody, protein C, protein S, antithrombin 3, von Willebrand assay, ristocetin cofactor, plasminogen activity, paroxysmal nocturnal hemoglobinuria panel, platelet function screen, and genetic studies were all normal. Obstetrical US showed single live intrauterine pregnancy, and given hemodynamic stability, she was managed medically. Discussion - This report highlights a case of recurrent AH in consecutive pregnancies, involving opposite adrenal glands and no identifiable hypercoagulable state, which has not been previously reported. During pregnancy, placental CRH stimulates the maternal pituitary gland, increasing ACTH, which subsequently leads to adrenal hypertrophy. The hypertrophied adrenal glands are prone to vascular congestion and can lead to AH. Pregnancy, being a hypercoagulable state, adds to the risk factor as well. AH should be included in the differential when evaluating abdominal pain in prenatal individuals. Emergent surgery and preterm delivery are warranted in patients with hemodynamic instability.

Differentiation of pathologic/neoplastic hypercortisolism (Cushing’s syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing’s syndrome): Letter to the Editor

I enjoyed reading Prof. Findling and Prof. Raff’s recent review article on hypercortisolism (1), and this letter provides further discussion on one sentence in that article. The review states that ‘CRH-binding protein also increases during pregnancy, which may prevent the stimulatory effects of placental CRH on the maternal pituitary gland (67 (2), 68 (3), 69 (4)).’ The references cited at the end of the aforementioned statement, however, do not report that plasma levels of CRH-binding protein increase during pregnancy, and indeed, CRH-BP plasma levels decrease in the last few weeks of pregnancy so the stimulatory effects of placental CRH on the maternal pituitary gland may be increased at this time. Sasaki and coworkers wrote, ‘CRH-binding protein did not increase during pregnancy’ (3) in reference to the paper by Suda and coworkers, which reported that the amount of binding of radiolabeled CRH to CRH-BP in pregnant women’s plasma (the plasma had been stripped of endogenous CRH) does not significantly change throughout pregnancy or become significantly different from non-pregnant controls (2). When endogenous CRH was not pre-stripped from plasma, levels of radiolabeled CRH binding to the CRH-BP stayed relatively stable for the first two trimesters, and then progressively decreased to reach approximately 40% of control non-pregnant levels shortly before parturition (2). The authors concluded that, (1) rises in CRH secretion from the placenta may have been displacing the radiolabeled CRH from the CRH-BP in later pregnancy plasma samples that did not have endogenous CRH removed, (2) the assay that they used does not show actual concentrations of CRH-BP and (3) the results suggest that hypothetically, even if there was a rise in CRH-BP levels at the end of pregnancy (noting that cortisol-binding protein levels show this pattern) that their assay did not reveal, it would be small (2).

Hormones Influencing Growth of the Fetus: A Review

Aim: To write a review on hormones influencing growth of the fetus. Background: The metabolic adaptations of pregnancy are regulated by hormones produced by placental and maternal pituitary glands. They regulate key physiological events essential for maintaining pregnancy and developing fetus for extra uterine life. Hormones influencing foetal growth are released by mother, placenta and foetus; they belong to growth hormone (GH)/ prolactin gene family, placental lactogens( PL) and prolactin related hormones. Placental hormones are peptides such as Chorionic Gonadotropins, placental lactogens; or Steroids such as Progestogens and Estrogens. In Primary Congenital Hypothyroidism (CH), the baby is born normal, but shows signs of hypothyroidism later. Deficiency of Human Chorionic Somatomammotropin results in decreased placental weight associated with Intra Uterine Growth Restriction (IUGR) leading to low birth weight babies. Studies have shown maternal deficiency of GH and thyroid hormones may not affect prenatal size of foetus. However, mutation of IGF I in mother inhibits GH action resulting in Small For Dates babies despite normal gestation period. These babies are immediately treated with Growth Hormone therapy on birth. Reason for the review: To have a better understanding of the close communication between placenta and foetus, involving complex physiological developmental regulatory mechanisms.

Placental hormones and the control of maternal metabolism and fetal growth

To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression. The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.

Pregnancy‐Induced Adaptation in the Neuroendocrine Control of Prolactin Secretion

During pregnancy, neuroendocrine control of prolactin secretion is markedly altered to allow a state of hyperprolactinaemia to develop. Prolactin secretion is normally tightly regulated by a short-loop negative-feedback mechanism, whereby prolactin stimulates activity of tuberoinfundibular dopamine (TIDA) neurones to increase dopamine secretion into the pituitary portal blood. Dopamine inhibits prolactin secretion, thus reducing prolactin concentrations in the circulation back to the normal low level. Activation of this feedback secretion by placental lactogen during pregnancy maintains relatively low levels of prolactin secretion during early and mid-pregnancy. Despite the continued presence of placental lactogen, however, dopamine secretion from TIDA neurones is reduced during late pregnancy. Moreover, the neurones become completely unresponsive to endogenous or exogenous prolactin at this time, allowing a large nocturnal surge of prolactin to occur from the maternal pituitary gland during the night before parturition. In this review, we describe the changing patterns of prolactin secretion during pregnancy in the rat, and discuss the neuroendocrine mechanisms controlling these changes. The loss of response to prolactin is an important maternal adaptation to pregnancy, allowing the prolonged period of hyperprolactinaemia required for mammary gland development and function and for maternal behaviour immediately after parturition, and possibly also contributing to a range of other adaptive responses in the mother.

Corticotropin Releasing Factor (CRF) Binding Protein: A Novel Regulator of CRF and Related Peptides

A 37-kDa corticotropin releasing factor (CRF) binding protein (CRF-BP) was purified from human plasma by repeated affinity purification and subsequently sequenced and cloned. The human and rat CRF-BP cDNAs encode proteins of 322 amino acids with one putative signal sequence, one N-glycosylation site, and 10 conserved cysteines. Human CRF-BP binds human CRF with high affinity but has low affinity for the ovine peptide. In contrast, sheep CRF-BP binds human and ovine CRF with high affinity. The CRF-BP gene consists of seven exons and six introns and is located on chromosome 13 and loci 5q of the mouse and human genomes, respectively. CRF-BP inhibits the adrenocorticotrophic hormone (ACTH) releasing properties of CRF in vitro. CRF-BP dimerizes after binding CRF and clears the peptide from blood. This clearance mechanism protects the maternal pituitary gland from elevated plasma CRF levels found during the third trimester of human pregnancy. CRF-BP is expressed in the brains of all species so far tested but is uniquely expressed in human liver and placenta. In brain, CRF-BP is membrane associated and is predominantly expressed in the cerebral cortex and subcortical limbic structures. In some brain areas CRF-BP colocalizes with CRF and CRF receptors. The protein is also present in pituitary corticotropes, where it is under positive glucocorticoid control, and is likely to locally modulate CRF-induced ACTH secretion. The ligand requirements of the CRF receptor and the CRF-BP can be distinguished in that central human CRF fragments, such as CRF (6-33) and CRF (9-33), have high affinity for CRF-BP but low affinity for the CRF receptor. The binding protein's ability to inhibit CRF-induced ACTH secretion can be reversed by CRF (6-33) and CRF (9-33), suggesting that ligand inhibitors may have utility in elevating free CRF levels in disease states associated with decreased CRF. Thus, by controlling the amount of free CRF which activates CRF receptors, it is likely that the CRF-BP is an important modulator of CRF both in the CNS and in the periphery.

Diethylstilbestrol-Induced Perinatal Lethality in the Rat. II. Perturbation of Parturition1

Evidence is presented suggesting that the fetolethal properties of diethylstilbestrol (DES) are indirect, mediated maternally through a perturbation of the normal mechanisms of parturition. Oral administration of the compound to Sprague-Dawley rats near Day 18 of pregnancy was shown to delay the onset of parturition, prolong labor, and induce dystocia, with a concomitant large increase in perinatal mortality. Exposure during Days 8-16 was without effect, whereas treatment in the Day 18-20 interval resulted in preterm delivery. Inability to initiate labor at term, accompanied by fetal death, also resulted from the administration of hCG on Days 16-18. The relative incidence of stillbirths in DES-exposed pups was markedly decreased by Caesarean delivery. The average weight of the maternal pituitary gland was not affected by treatment, whereas maternal adrenal glands were 30% larger. Maternal blood levels of corticosterone were not significantly elevated, however. The average number of follicles on Day 21 was significantly reduced by DES, and a histological analysis failed to demonstrate a luteotropic effect of the compound. In dams treated on Days 8-18, serum progesterone was reduced by as much as 60%, and total estrogens were 32% lower than in controls. We conclude that DES acts in the rat to depress the preterm levels of steroid hormones, which leads to a failure of uterine contraction accompanied by placental detachment and fetal death.

Evidence that luteinizing hormone from the maternal pituitary gland may promote antepartum release of relaxin, luteolysis, and birth in rats.

The role of the maternal pituitary gland and LH in the regulation of the release of relaxin from the onset of the light phase on day 21 of pregnancy (day 21) until delivery (herein designated the antepartum period) was examined in rats. Serum relaxin levels were determined in rats hypophysectomized (HYPOX) or sham hypophysectomized (SHAM) on day 14. In SHAM rats, the elevated serum relaxin levels that occurred during the light phase of days 21 and 22 coincided with a rapid decline in serum progesterone to basal levels, and relaxin levels then declined markedly throughout the 18- to 24-h before delivery. During the antepartum period HYPOX rats differed from SHAM rats in the following ways: 1) mean serum relaxin levels were higher immediately before the antepartum period (day 20) and remained at the maximal levels the sham-operated animals experienced throughout the ensuing antepartum period; 2) elevations in relaxin levels generally occurred in individual rats; however, they usually occurred later than day...

Timing of termination of nocturnal prolactin surges in pregnant rats as determined by the number of fetuses.

In female rats bearing an average litter of 10+/-0.28 fetuses, pituitary prolactin is secreted in a pattern of two daily surges during the first 10 days of pregnancy only. When the number of fetuses was experimentally reduced, prolactin surges continued for a longer period and pregnancy was correspondingly lengthened. The relationship found between a reduced number of fetuses, and delay in termination of prolactin surges further supports the view that, during pregnancy, rat placental lactogen exerts a major influence in inhibiting secretion of prolactin by the maternal pituitary gland. The constant relationship found in all groups between termination of nocturnal surges of prolactin and parturition indicates that it is the interval between implantation and termination of prolactin surges which is prolonged in female rats with small litters.

Effects of prepartal stress on postpartal nursing behavior, litter development and adult sexual behavior

Sprague-Dawley rats were exposed to the stress of restraint, heat and bright lights three times daily from Days 14 to 22 of gestation. Because prepartal stress did not markedly disturb the mother's retrieving and crouching behavior, disturbances in postpartal nursing behavior do not seem to account for the abnormal sexual behavior of male offspring as adults. The most significant finding was that litter weights were reduced, not only at birth, but for 3 weeks thereafter, suggesting that prepartal stress not only altered the pups in utero but also affected postpartal milk synthesis. The possibility emerges that prepartal stress may alter adult sexual behavior in males by modifications in fetal and/or maternal pituitary glands.

Blood Levels of 17-Hydroxycorticosteroids (17-OHCS) During Labor of Human Pregnancy.

Summary1. Blood levels of 17-OHCS were studied at intervals during parturition in normal pregnancy. 2. Early in labor, a rise in levels above those found in late pregnancy was noted, with further rise between first and second stages. These high levels were maintained until after the end of 3rd stage. In most cases studied, levels were still well above normal on 4th or 6th postpartum day. 3. There seems to be a relation between length of labor and rise in plasma 17-OHCS. Labors of longer than 6 hours deviation were accompanied by high levels of these hormones. 4. Maximum values observed in labor approached those noted after exogenous ACTH stimulation during late pregnancy, indicating nearly maximal output of these hormones by the adrenal cortex. 5. The mechanisms by which labor stimulated the maternal pituitary gland have been discussed.