The opiate-like peptide beta-endorphin and adrenocorticotropin are concomitantly secreted in increased amounts by the adenohypophysis in response to acute stress or long-term adrenalectomy as well as in vitro in response to purified corticotropin releasing factor and other secretagogues. Conversely, administration of the synthetic glucocorticoid dexamethasone inhibits the secretion of both adrenocorticotropin and beta-endorphin. Thus, both hormones possess common and identical regulatory mechanisms and there may be a functional role for circulating beta-endorphin.

http://science.sciencemag.org/content/sci/197/4311/1367.full.pdf

beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland

I. Introduction II. Synthesis and Secretion of Progesterone III. The Progesterone Receptor A. PR expression and regulation IV. Progesterone Regulation of Gene Expression in the Uterus, Ovary, and Chick Oviduct A. Progesterone effects on proliferation and decidualization in the uterus during the menstrual cycle B. Progesterone regulation of insulin-like growth factor (IGF) pathways in the endometrium C. Control of ovulation D. Implantation, uterine proliferation, and early pregnancy E. Myometrial contractility F. Chick oviduct V. Progesterone Action in the Breast A. Effect of progesterone on proliferation of the normal breast B. Progesterone regulation of genes associated with cell cycle progression C. Progesterone regulation of growth factors and growth factor receptors in the breast D. Markers of progestin action in the breast E. Progesterone effects on lactation VI. Progesterone Effects in the Brain VII. Progesterone Effects on Bone VIII. Antiestrogen Action of Progesterone A. Inhibition of ER expressio...

http://hormonebalance.org/images/documents/Graham%2097%20Physioloical%20action%20of%20Progesterone%20EnRev_1311166255.pdf

Physiological action of progesterone in target tissues.

We have examined factors concerned with the maintenance of uterine quiescence during pregnancy and the onset of uterine activity at term in an animal model, the sheep, and in primate species. We suggest that in both species the fetus exerts a critical role in the processes leading to birth, and that activation of the fetal hypothalamic-pituitary-adrenal axis is a central mechanism by which the fetal influence on gestation length is exerted. Increased cortisol output from the fetal adrenal gland is a common characteristic across animal species. In primates, there is, in addition, increased output of estrogen precursor from the adrenal in late gestation. The end result, however, in primates and in sheep is similar: an increase in estrogen production from the placenta and intrauterine tissues. We have revised the pathway by which endocrine events associated with parturition in the sheep come about and suggest that fetal cortisol directly affects placental PGHS expression. In human pregnancy we suggest that cortisol increases PGHS expression, activity, and PG output in human fetal membranes in a similar manner. Simultaneously, cortisol contributes to decreases in PG metabolism and to a feed-forward loop involving elevation of CRH production from intrauterine tissues. In human pregnancy, there is no systemic withdrawal of progesterone in late gestation. We have argued that high circulating progesterone concentrations are required to effect regionalization of uterine activity, with predominantly relaxation in the lower uterine segment, allowing contractions in the fundal region to precipitate delivery. This new information, arising from basic and clinical studies, should further the development of new methods of diagnosing the patient at risk of preterm labor, and the use of scientifically based strategies specifically for the management of this condition, which will improve the health of the newborn.

/pdf/endocrine-and-paracrine-regulation-of-birth-at-term-and-4igz1kdkru.pdf

Endocrine and paracrine regulation of birth at term and preterm

I. Introduction II. Development A. Embryonic adrenal development B. Fetal adrenal development C. Neonatal adrenal development D. Growth E. Functional development 1. Ontogeny of steroidogenic activity 2. Functional zonation and ontogeny of steroidogenic enzyme expression 3. Responsiveness to ACTH III. Regulation A. The fetal pituitary and ACTH B. Growth factors 1. Basic fibroblast growth factor (bFGF) 2. Epidermal growth factor (EGF) 3. Insulin-like growth factors I and II (IGF-I and IGF-II) 4. Activin/inhibins 5. TGFβ C. Nuclear receptors/transcription factors D. Placental factors 1. Human CG (hCG) 2. Placental CRH and ACTH 3. Indirect effect of placental glucocorticoid metabolism 4. Placental estrogens IV. Physiology A. Placental estrogen formation B. Timing of parturition and fetal maturation V. Summary

/pdf/developmental-and-functional-biology-of-the-primate-fetal-3a8vv49pkn.pdf

Developmental and functional biology of the primate fetal adrenal cortex.

Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20408

Human prostate cancer risk factors.

Relaxin is a peptide hormone whose A- and B-chains are derived by posttranslational cleavage from a single 185-amino acid preprorelaxin. Two genes in the human genome (H1 and H2) code for two polypeptides significantly different in amino acid sequence. The full spectrum of biological activities of these two polypeptides has not been examined, but transcription appears to be limited to the H2 relaxin gene in the human corpus luteum. Relaxin is also synthesized by the human decidua, placental trophoblast, and prostate gland; therefore, the expression of the human relaxin genes in these tissues has been examined using the reverse transcription polymerase chain reaction. The mRNA from decidua, placental trophoblast, and prostate was reverse transcribed and then amplified by polymerase chain reaction, using a series of oligonucleotide primers that were specific for but would not distinguish between human H1 and H2 relaxins. Using mRNA from these tissues, two amplified cDNA species were detected, whose identities were confirmed by Southern blots, HpaI and HpaII restriction enzyme analysis, and dideoxy sequencing. We have confirmed that the corpus luteum does not contain detectable H1 relaxin mRNA. However, we demonstrated for the first time relaxin H1 gene expression in the decidua, placental trophoblast, and prostate, and we have also shown that there are marked tissue differences in the relative amounts of expression of the H1 and H2 relaxin mRNA forms. The functional significance is unknown, but if both mRNAs are translated, differential expression of the two genes may result in tissue-specific differences in the production of these relaxins as well as in their binding and actions.

Expression of the human relaxin h1 gene in the decidua, trophoblast, and prostate

The concentration and affinity of the receptors for relaxin in the myometrium of rats were compared during the estrous cycle, in pregnancy, after ovariectomy, and after estrogen and/or relaxin administration. The concentration of the myometrial relaxin receptors in cyclic rats appeared to be related to plasma estrogen levels. Ovariectomy of cyclic animals resulted in the disappearance of receptors by 7 days after surgery. Recovery of the receptors was demonstrable upon estrogen administration to these animals. The response of the uterus to estrogen was biphasic and dependent on the time of exposure to the hormone in vivo. Relaxin receptor concentration increased 5- and 30-fold relative to those at estrus and proestrus within 24 h of the administration of 5 and 200 μg of the steroid, respectively, with no significant change in the receptor's affinity constant. The number of myometrial receptors found in pregnancy were unrelated to the known changes in plasma estrogen levels. However, during late pregnancy,...

Relaxin receptor in the rat myometrium: regulation by estrogen and relaxin.

Immunocytochemistry and Northern analysis were used to show that relaxin is a product of intrauterine tissues of pregnancy. In addition, tissues from a patient without ovarieshad similar results on both immunocytochemistry and Northern analysis as tissues from intact patients. The parietal decidua was clearly the major source of relaxin within the uterus and the relaxin mRNA (1.2 kilobases) from this tissue was detected with a 48-mer oligonucleotide probe designed to hybridize with both H1 and H2 relaxin gene transcripts. The mRNA isolated fromthe placental trophoblast was slightly smaller (1.1 kilobases), and the placental basal plate which has both maternal and fetal cells contained relaxin mRNAs of both sizes. Two monoclonal antibodies (Mabs) raised to synthetic human relaxin (H2) gave different patterns of localization in the fetal membranes,membranes, decidua and placenta. One Mab (RLX8) stained the chorioniccytotrophoblast in the fetal membranes and all of the cells in the placental basal plate. The...

Human Relaxin in the Amnion, Chorion, Decidua Parietalis, Basal Plate, and Placental Trophoblast by Immunocytochemistry and Northern Analysis*

The hormone synthesis and release in vitro from the adenohypophysis of 40 normal human fetuses was studied by radioimmunoassay and protein incorporation of C14-l-leucine. Within the first 20 days in vitro, the release of GH, prolactin (PRL), LH, FSH, TSH, ACTH and MSH decreased to low or undetectable levels. The production of PRL and MSH, after the initial fall, spontaneously increased with time in culture to sustained and elevated levels. For all the hormones the quantity released was related to the gestational age of the donor fetus. In the cases of LH and FSH the hormonal release was not only related to the age of the fetus but also to the sex. The duration of FSH release in vitro was significantly longer (p > 0.005) for female pituitary cultures than for males. The release of pituitary hormones was detected as early as 5 weeks fetal life. In some fetuses, abnormal release of certain hormones in vitro could be relatd to demonstrable fetal abnormalities. These results indicate that the fetal pi...

Hormone Synthesis and Release from Human Fetal Adenohypophyses in Vitro

Relaxin (Rlx) is shown in vitro to increase the release of plasminogen activator (PA) activity from granulosa cells obtained from 28-day-old rats after priming 48 h before with PMSG. Priming with PMSG was essential for the subsequent marked increase in PA by the addition of Rlx to these cells in vitro. Under the same conditions Rlx also increased the release of both total collagenase and total proteoglycanase activities but not of β-glucuronidase activity. The total collagenase and proteoglycanase activities of control cells are made up of essentially equal amounts of their respective active and latent enzymes. Rlx stimulation increases the amounts of the respective active enzymes while the latent collagenase and proteoglycanase activities are unchanged or decreased, respectively. The enzyme β-glucuronidase was not stimulated by Rlx and appears not to be involved in follicular proteoglycan degradation. Granulosa cells harvested from preantral follicles responded most to FSH by PA production whereas cells ...

F. C. Greenwood

Papers

Expression of the human relaxin h1 gene in the decidua, trophoblast, and prostate

Relaxin receptor in the rat myometrium: regulation by estrogen and relaxin.

Human Relaxin in the Amnion, Chorion, Decidua Parietalis, Basal Plate, and Placental Trophoblast by Immunocytochemistry and Northern Analysis*

Hormone Synthesis and Release from Human Fetal Adenohypophyses in Vitro

Relaxin increases the release of plasminogen activator, collagenase, and proteoglycanase from rat granulosa cells in vitro.