Artificial lactation by exogenous hormone treatment in non-pregnant sows.

This study aimed to determine if lactation can be induced by exogenous hormonal treatment in non-pregnant sows. In experiment 1, pseudopregnant animals were divided into four groups and given: 1) 5 mg of estradiol dipropionate (EDP) 5 days before (n = 4), 2) 5 mg of EDP 10 days before (n = 3), 3) 10 mg of EDP 5 days before (n = 3) or 4) 10 mg of EDP 10 days (n = 3) before PGF2α treatment. Artificial lactation was induced in seven pseudopregnant sows (53.8%) by exogenous hormonal treatment. There was no significant effect of either an increased EDP dosage or interval from the EDP treatment to PGF2α treatment on the induction rate of artificial lactation. In experiment 2, milk samples were collected from artificial lactating and natural lactating sows (n = 6). IgG and IgA levels in the milk collected from both groups were significantly associated with time during the experimental period. Milk IgG levels 24 h after PGF2α treatment in artificial lactating sows were higher than those in the colostrum of lactating sows. In experiment 3, hormonal profiles in pseudopregnant sows with (n = 3) or without (n = 3) EDP treatment were determined. There was a significant difference in estradiol-17ß levels on days 8, 7 and 5 before PGF2α treatment between groups. Progesterone and prolactin concentrations did not differ between groups. The present study revealed for the first time that lactation could be induced by exogenous hormonal treatment in non-pregnant sows and that the milk collected from these sows contained high immunoglobulin levels.

[Impacts on thepregnancy outcome in the mice of controlled ovarian hyperstimulation treated with acupuncture at different time points].

OBJECTIVE: To explore the optimal time of acupuncture intervention in the assisted reproduction. METHODS: One hundred and twenty female mice and 60 male mice were collected. 20 female mice were selected in the natural period group and the rest 100 female mice were prepared as the model of controlled ovarian hyperstimulation (COH). The model mice were randomized into a COH group, a down-regulation group, a gonadotropins (Gn) start group, an injection of human chorionic gonadotropin (HCG) group and an embryo culture group, 20 mice in each one. The donor mice and receptor mice were subdivided in each group, 10 mice in each subgroup. One week before the experiment, vas deferens ligature was done in 30 male mice and the other 30 male mice did not receive ligature. In the down-regulation group, the Gn start group, the HCG injection group and the embryo culture group, electroacupuncture (EA) was applied to "Guanyuan" (CV 4), "Zhongji" (CV 3) and "Sanyinjiao" (SP 6) at the time points accordingly. EA stimulation was in the condition of continuous wave, 2 Hz and 1 mA. No inter-vention was given in the natural period group and the COH group. On the day of HCG injection, the donor mice and the non-ligatured male mice were put in the same cage of each group. The fertilized ovum was collected with the date of fertilization marked and was fostered in the incubator. At the ratio of 1:1, the receptor mice and ligatured mice were put in the same cage in each group. The vaginal plug was examined in the next morning. The pseudopregnancy was marked with the date of plug observed. In the 68th hour of embryo culture, the embryo of the donor was shifted to the receptor on the same day when the plug was observed. The clinical pregnancy rate and embryo imbed site number were observed. RT-PCR assay was adopted to determine the expression of insulin-like growth factor-1 (IGF-1) mRNA in endometrium. RESULTS: In the COH group, the pregnancy rate, average imbed site number and endometrial IGF-1 mRNA expression were all significantly lower than those in the natural period group (all P<0.01). After EA treatment, in the Gn group, the HCG injection group and the embryo culture group, the pregnancy rates were higher significantly than those in the COH group (P<0.05, P<0.01). In the HCG injection group, the average imbed site number and IGF-1 mRNA expression were increased apparently as compared with those in the COH group (both P<0.01), better than those in the Gn group and the embryo culture group (all P<0.01). CONCLUSIONS: In the treatment with acupuncture combined with IVF-ET for infertility, the intervention of acupuncture on the day of HCG injection is the optimal time point. It increases the secretion of endometrial IGF-1 so as to improve the clinical pregnancy rate, the mean imbed site number and the embryo implantation.

Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.

All mammalian uteri have luminal (LE) and glandular epithelia (GE) in their endometrium. The LE mediates uterine receptivity and blastocyst attachment for implantation, and the GE synthesize and secrete or transport bioactive substances involved in blastocyst implantation, uterine receptivity, and stromal cell decidualization. However, the mechanisms governing uterine epithelial development after birth and their function in the adult are not fully understood. Here, comprehensive microarray analysis was conducted on LE and GE isolated by laser capture microdissection from uteri on Postnatal Day 10 (PD 10) and day of pseudopregnancy (DOPP) 2.5 and 3.5. This data was integrated with analysis of uteri from gland-containing control and aglandular progesterone-induced uterine gland knockout mice from PD 10 and DOPP 3.5. Many genes were expressed in both epithelia, but there was greater expression of genes in the LE than in the GE. In the neonate, GE-expressed genes were enriched for morphogenesis, development, migration, and retinoic acid signaling. In the adult, LE-expressed genes were enriched for metabolic processes and steroid biosynthesis, whereas retinoid signaling, tight junction, extracellular matrix, and regulation of kinase activity were enriched in the GE. The transcriptome differences in the epithelia support the idea that each cell type has a distinct and complementary function in the uterus. The candidate genes and regulatory networks identified here provide a framework to discover new mechanisms regulating development of epithelia in the postnatal uterus and their functions in early pregnancy.

Variation in maternal care influences ventromedial hypothalamus activation in the rat.

Natural variation in maternal care in the rat is an important source of individual differences in the female neuroendocrine system and sexual behaviours. Thus, females reared by low licking and grooming (LG) mothers are sexually more receptive to males, showing higher lordosis ratings, and are more motivated to mate compared to female offspring of high LG mothers. In the present study, we investigated the effect of natural variations in maternal care on the ventrolateral part of the ventromedial hypothalamus (VMHvl) cell population and on the reproductive success of the female rat. Immunohistochemistry for phosphorylated oestrogen-receptor (pER) α and progesterone receptor (PR) were used to study the VMHvl of female offspring of high and low LG mothers at pro-oestrus and dioestrus. A second experiment investigated sexual behaviour and the effect of mating on c-Fos expression in the VMHvl of pro-oestrus and ovariectomised high and how female offspring. Lastly, we investigated the maternal effect on the establishment of the progestational state. A greater number of VMHvl pERα immunoreactive cells was found in the pro-oestrous female offspring of low LG mothers and PR was most abundant at pro-oestrus compared to dioestrus in both high and low LG females. Interestingly it is the less receptive high females that show the greater c-Fos expression in the VMH after mating in the pro-oestrous group. The difference in c-Fos expression after mating disappeared when the two groups were ovariectomised and received steroid replacement. Finally, low LG female offspring reached pseudopregnancy more often when receiving only seven intromissions at a 5-min interval compared to high LG females. Lower levels of maternal care may favour the reproductive success of low LG offspring by increasing pERα and oestrogen-dependent lordosis behaviour and lowering c-Fos after mating, resulting in inhibition of termination of oestrus.

Progesterone receptor immunoreactivity differs in the uterus of pseudopregnant and medroxyprogesterone acetate-treated rabbits.

Progesterone receptor (PR) plays an important role in mammals pregnancy which is characterized by greater progesterone plasma concentrations. We assessed PR protein distribution in the rabbit uterus by immunohistochemistry in two progestational conditions: pseudopregnancy (intact adult animals treated with hCG) and after application of a synthetic progestin, medroxyprogesterone acetate (MPA), to ovariectomized animals (OVX). PR immunoreactivity in uterine epithelium of pseudopregnant rabbits was increased in relation to non-pseudopregnant (NP) rabbits. Amounts were similar on Days 1, 3, and 5 of treatment, and was greater on Day 7 (P<0.001). In contrast, a significant diminution in PR immunoreactivity was observed in stroma cells from Days 1 to 7 (P<0.001). In OVX rabbits treated with MPA, an increase in PR immunoreactivity was observed in the uterine epithelium on Days 1 to 5 of treatment, reaching a maximum on Day 3 (P<0.001). In contrast, in stromal cells a diminution in PR immunoreactivity was observed when compared to the OVX group on Days 1, 3 and 7 of MPA treatment (P<0.001), and there was a slight increase on Day 5. Results suggest a differential time course and tissue specific immunoreactivity for PR in the uterus of the rabbit in two progestational conditions. The present study indicated synthetic progestins have different mechanisms of receptor regulation than those of natural hormones and it should be taken into account in reproductive applications.

[Recurrent pseudocyesis with polydipsia: a case report]. / Grossesse délirante récurrente avec polydipsie: à propos d'un cas.

INTRODUCTION: Pseudocyesis is an imaginary pregnancy resulting from a strong desire or need for motherhood. Pseudocyesis has become increasingly rare in many parts of the world in which accurate pregnancy tests have become widely available. Cultures that place high value on pregnancy, or that make close associations between fertility and a person's worth, still have high rates of the disorder. A woman may believe in her pregnancy to the point of delusion and show acute depression when no baby is born. CASE-REPORT: This report describes a case of recurrent pseudocyesis and polydipsia in a 49-year-old woman. She was an illiterate housewife who had been married since she was 21 years old. Four years later, she divorced because of a problem of sterility. She got remarried, five years later, and the couple had no child. The patient was admitted into the Obstetric Unit thinking that she was about to give birth. She presented all the symptoms of true pregnancy. She had abdominal distension, amenorrhea, mammary tension, nausea and vomiting, and weight gain. She claimed to have felt foetal movements. Other than this, she exhibited a polydipsia syndrome. These symptoms had evolved over 20 months. The patient had previously presented six similar episodes. All these episodes were identical. The length of these episodes varied between three and five months, after which all the signs disappeared progressively. The patient had never consulted for these symptoms before the present episode. During her stay in the Obstetric Unit, she benefited from a complete gynaecological examination, including pelvic ultrasound examinations, and laboratory tests, notably hormone assays (FSH, LH, prolactin, ss-HCG) and serum electrolyte levels. A primary sterility and menopause were confirmed. Otherwise, the psychiatric assessment confirmed the delusion of pregnancy and the presence of a depressive syndrome. The patient reported that she was possessed. She explained the normality of the imagery and laboratory tests by the intervention of the demons that hid the foetus and modified the results. DISCUSSION: The contribution of psychological and physiological factors in the development of the delusion of pregnancy, possession and polydipsia, and the possible interactions between the two phenomena are discussed.

Uterotrophic, fetotoxic and abortifacient effect of a Malaysian variety of Plumbago rosea L. on isolated rat uterus and pregnant mice.

Traditionally Plumbago rosea L. is used as an abortifacient in the Southeast Asian region. Methanolic root extract of a local species of Plumbago rosea L. was studied to evaluate its traditional antifertility claim. Interestingly, it was found to possess dose related inhibitory effect on uterine contractile responses elicited by oxytocic agents on isolated uteri of pregnant and pseudo-pregnant rats. Furthermore, it was found to possess significant (p < 0.05) fetotoxic activity along with mild abortive potential in pregnant mice when given orally at high doses (400 and 800 mg kg(-1)) once daily for ten days starting from day 10 of gestation. The results derived indicated possible presence of utero-active compound (s) in this plant that inhibited oxytocic agents induced uterine motility. Moreover, pronounced fetotoxic and mild abortifacient potentials observed at higher doses in pregnant mice might support its accredited traditional use to avoid unwanted pregnancy.

Decidualization induces the expression and activation of an extracellular protease neuropsin in mouse uterus.

Uterine decidualization is accompanied by the remodeling of the cell-matrix and cell-cell interactions around the endometrial stromal cells to allow an appropriate invasion of trophoblasts. This remodeling is thought to require the proteolysis of extracellular matrix proteins or cell adhesion molecules; however, the molecular mechanism remains poorly understood. In this study, decidualization induced the expression and activation of an extracellular serine protease neuropsin in the mouse uterus. Although nonpregnant uteri contained little neuropsin, the protein content and enzymatic activity increased markedly and peaked at the midgestational period in pregnant uteri. Neuropsin expression and activity was also upregulated in artificially induced deciduomata but not in nondecidualized pseudopregnant uteri. Neuropsin is the first extracellular protease to show the evident induction of expression and activity by decidualization and might contribute to the remodeling of extracellular components after decidualization.

Basigin expression and hormonal regulation in mouse uterus during the peri-implantation period.

Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, has been shown to be essential for fertilization and implantation. The aim of this study was to determine the expression and hormonal regulation of basigin gene in mouse uterus during the peri-implantation period. Basigin immunostaining and mRNA were strongly localized in luminal and glandular epithelium on day 1 of pregnancy and gradually decreased to a basal level from day 2-4 of pregnancy. Basigin mRNA expression in the sub-luminal stroma was first detected on day 3 of pregnancy and increased on day 4 of pregnancy. On day 5 of pregnancy, the expression of basigin protein and mRNA was only detected in the implanting embryos, and the luminal epithelium and sub-luminal stroma surrounding the embryos. A similar expression pattern of basigin was also induced in the delayed-implantation uterus which was activated by estrogen injection. On day 6-8 of pregnancy, although a basal level of basigin protein was detected in the secondary decidual zone, basigin mRNA expression was strongly seen in this location. Basigin mRNA was also highly expressed in the decidualized cells under artificial decidualization. Estrogen significantly stimulated basigin expression in the ovariectomized mouse uterus. A high level of basigin immunostaining and mRNA was also seen in proestrus and estrus uteri. These results suggest that basigin expression is closely related to mouse implantation and up-regulated by estrogen.

Gestation et lactation nerveuses de la chienne / Nervous pregnancy and nursing of the female dog

Dans les meutes de loups, il arrive souvent que plisieurs femelles allaitent les petits d'une même portée. Cela n'est possible que si elles ont du lait, malgré le fait qu'elles n'aient point mis bas, c'est le phénomène de la "lactation nerveuse". Tout se passe comme si les autres louves avaient... (AU)

Induction of glucose-regulated protein 78 in rat uterine glandular epithelium during uterine sensitization for the decidual cell reaction.

Endometrial receptivity for implantation and sensitization for decidualization in rodents is a transient state under the control of the ovarian steroids estrogen and progesterone. It is unclear, however, what molecular events mediate the onset of uterine receptivity. Messenger RNA differential display was performed on endometrial RNA from ovariectomized rats differentially sensitized for decidualization. Maximally sensitized uteri were at the equivalent of Day 5 of pseudopregnancy, and temporally nonsensitized uteri at Day 4 or 6; hormonally nonsensitized uteri were from animals on Day 5 treated with low or high doses of estradiol on Day 4. A cDNA with endometrial expression restricted to maximally sensitized uteri was isolated, cloned, and sequenced. The cDNA matched the sequence for glucose-regulated protein 78 (GRP78), a heat shock 70-related protein that resides in the lumen of the endoplasmic reticulum (ER) and has roles in several cellular processes including multimeric protein assembly, the degradation of proteins, and the storage and regulation of ER luminal calcium. Northern blot analysis indicated a dramatic increase in GRP78 mRNA levels restricted to the sensitized, Day 5 endometrium, suggesting a role in the onset of the sensitized phase. In situ hybridization and immunohistochemistry experiments localized the up-regulation of GRP78 within the receptive endometrium to the glandular epithelium.

Rescue of the corpus luteum and an increase in luteal superoxide dismutase expression induced by placental luteotropins in the rat: action of testosterone without conversion to estrogen.

The superoxide radical and its scavenger, superoxide dismutase (SOD), play important roles in the regulation of corpus luteum function. The present study was undertaken to investigate whether SOD is related to pregnancy-induced maintenance of corpus luteum function. Placentae obtained from rats on Day 12 of pregnancy were incubated for 24 h, and the supernatant was used as placental luteotropins. Pseudopregnant rats were given the placental incubation medium from Day 9 to Day 12 of pseudopregnancy. The treatment significantly increased serum progesterone concentrations on Day 12 of pseudopregnancy. Both activities and mRNA levels of copper-zinc SOD (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in the corpus luteum were also increased on Day 12 of pseudopregnancy. Treating the placental incubation medium with charcoal significantly eliminated the stimulatory effects of placental incubation medium on serum progesterone concentrations and luteal Mn-SOD expression, but not on Cu,Zn-SOD expression. The inhibitory effect of the charcoal treatment on luteal Mn-SOD expression was reversed by supplementation with testosterone or dihydrotestosterone (DHT), but serum progesterone concentrations were recovered only by DHT. Testosterone or DHT alone had no effect on serum progesterone concentrations and luteal SOD expression. In conclusion, placental luteotropins increased SOD expression in the corpus luteum and stimulated progesterone production, suggesting that SOD is involved in the maintenance of the corpus luteum function by placental luteotropins. In addition, androgen, with other placental luteotropins, acted to stimulate progesterone production and Mn-SOD expression in pseudopregnant rats.

26-cholesterol hydroxylase in rat corpora lutea: A negative regulator of progesterone secretion.

From a subtracted cDNA library of rat luteal tissue, where cDNA fragments in functional luteal tissue were subtracted from those in regressing luteal tissue, a cDNA clone corresponding to 26-cholesterol hydroxylase (P450(C26)) was obtained. It is known that P450(C26) catalyzes the conversion of cholesterol to 26-hydroxycholesterol, which blocks cholesterol utilization in the cell, and that 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone to an inactive steroid, 20alpha-dihydroprogesterone (20alpha-OHP). Thus, using pseudopregnant rats as a model, physiological cooperation of P450(C26) and 20alpha-HSD in the reduction of progesterone release toward the end of the luteal phase was evaluated. Levels of P450(C26) and 20alpha-HSD mRNA were examined in corpora lutea from pseudopregnant rats by Northern blot or reverse transcription-polymerase chain reaction or both. P450(C26) mRNA was ubiquitously expressed in corpora lutea, and its expression increased toward the end of pseudopregnancy, while 20alpha-HSD was expressed in all corpora lutea on Day 16 (Day 0 = the day of after cervical stimulation) but not detected before Day 10. An inhibitor of 20alpha-HSD, STZ26 (D-homo-16-oxa-4-androstene-3,16alpha-dione), was administered at various doses to rats from Day 12 to 20, effectively suppressing the elevation of 20alpha-OHP in a dose-dependent manner but not the depletion of progesterone completely. The expression of P450(C26) mRNA was increased as STZ26 dose increased, which negatively correlated with the progesterone levels. These results strongly suggest that P450(C26) cooperated with 20alpha-HSD in the reduction of progesterone release from the rat luteal tissue at the end of the functional luteal phase.

Gelatinases A and B and tissue inhibitors of metalloproteinases 1, 2, and 3 during in vivo and in vitro decidualization of rat endometrial stromal cells.

An important event during decidualization is the remodeling of the extracellular matrix, an event controlled by the balance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A putative regulator of decidualization is prostaglandin E2 (PGE2). The present study shows that endometrial mRNA levels for TIMPs 1, 2, and 3 were increased while gelatinase A levels remained unchanged and gelatinase B levels decreased during oil-induced decidualization. The production of TIMPs 1, 2, and 3 and gelatinases A and B during in vitro decidualization was examined, as was the role of PGE2 as a regulator. Ovariectomized rats were given a regimen of estrogen and progesterone, which sensitized their uteri for decidualization, at which time endometrial stromal cells were isolated and cultured in serum-free conditions for 72 h. Northern blot analyses indicated the presence of the mRNAs for TIMPs and gelatinases, while reverse zymography and zymography showed the presence of their proteins. PGE2 decreased mRNA levels for TIMP-1 and gelatinase A but had no effect on gelatinase B or TIMPs 2 and 3. Indomethacin had no effect on any of the transcripts. These data indicate that rat endometrial stromal cells undergoing decidualization in vitro secrete gelatinases and TIMPs, and suggest that PGE2 may play a role in regulating tissue remodeling during decidualization.

Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy.

In the mouse, the attachment reaction between the blastocyst trophectoderm and the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of pregnancy and is rapidly followed by transformation of stromal cells into decidual cells (decidual cell reaction). This process can also be induced experimentally (deciduoma) by intraluminal oil infusion in the uterus on day 4 of pseudopregnancy. The decidual cell reaction is associated with up- and down-regulation of many genes in a cell-specific manner. Using mRNA differential display, we identified cyclin D3 as one of the genes that is upregulated in the uterus at the sites of blastocyst apposition during the attachment reaction. The levels of expression were low in the morning of days 1-4 as determined by Northern hybridization. In situ hybridization analysis showed that on days 1 and 2, signals were primarily localized in uterine epithelial cells, while signals were detected in both the stromal and epithelial cells on days 3 and 4. In contrast, with the initiation and progression of decidualization on days 5, 6 and 7, the levels of cyclin D3 mRNA were remarkably upregulated in stromal cells both at the mesometrial and the antimesometrial poles. However, on day 8, signals were primarily localized in stromal cells at the mesometrial decidual bed. Implanting blastocysts on these days also expressed cyclin D3 mRNA. In the progesterone-treated delayed implanting mice, the uterine levels of cyclin D3 mRNA were modest at the sites of blastocyst apposition, but were upregulated with the onset of implantation by estradiol-17beta. However, the decidual expression of cyclin D3 mRNA was not dependent on the presence of blastocysts, since increased expression also occurred in experimentally induced deciduoma in the absence of blastocysts. The importance of cyclin D3 in decidualization was further examined in Hoxa-10-deficient mice which show defective decidualization. The expression of cyclin D3 mRNA in Hoxa-10(-/-) uteri on day 5 was severely compromised after application of a deciduogenic stimulus on day 4 of pseudopregnancy. Collectively, the results suggest that cyclin D3 could be important for the process of decidualization.

Arrested pregnancy syndrome in Haiti: findings from a national survey.

This report describes findings from a national survey of pregnant women in Haiti regarding the social epidemiology of pedisyon (perdition), or "arrested pregnancy syndrome," a condition believed to be associated with infertility. Data collected on mortality of respondents' sisters were used to indirectly measure the prevalence of this culture-bound syndrome in the adult female population and to compare its distribution in urban and rural areas. Perdition appears to be a fairly common event that affects a large proportion of Haitian women. Reported cases of pedisyon were significantly higher in urban areas, which also differed from rural areas on respondent education, economic status, use of prenatal care, and fertility. No differences were found on sociodemographic, health, or fertility variables when women reporting perdition deaths were compared with women who reported other sister deaths. The utility and limitations of the proxy respondent method are discussed. Possible explanations for the higher rate of pedisyon among urban Haitian women are discussed, and suggestions are made for future research on arrested pregnancy syndrome.

Semicircadian rhythm of dopamine release in the mediobasal hypothalamus in awake rats during pseudopregnancy: evidence that a thyrotropin-releasing hormone analogue stimulates dopamine release and thereby inhibits prolactin secretion.

The release of dopamine (DA) from tuberoinfundibular (TIDA) neurons during prolactin (PRL) surge and nonsurge periods and the effects of the thyrotropin-releasing hormone (TRH) analogue CG 3703 on DA and PRL secretion were studied in awake pseudopregnant (PSP) rats by simultaneous measurement of extracellular DA levels in the mediobasal hypothalamus (MBH) by means of microdialysis and of plasma PRL concentrations by radioimmunoassay of PRL in blood sampled from a permanent heart cannula. Since basal DA levels were low, the experiments were performed under local infusion of the reuptake inhibitor nomifensine (5 mumol/l), which increased extracellular DA levels 5-fold around the probe, but did not affect the occurrence of the nocturnal PRL surge on day 7-8 of PSP. Under nomifensine conditions, during the interphase (18.00-1.00 h) plasma PRL levels were low (< 50 ng/ml), while the DA release from TIDA neurons was elevated (approximately 250%) relative to the DA values measured during the phase when the nocturnal PRL surge occurred (100%; 1.00-12.00 h; plasma PRL levels were elevated to approximately 300 ng/ml). Thus, semicircadian rhythms were detected both for DA and PRL, which were broadly reciprocal in timing. The TRH analogue CG 3703 (100 and 500 micrograms/animal i.v.), when administered at 00.00 h, dose-dependently increased extracellular DA levels (to 300 and 500% of pretreatment values, respectively) and postponed the PRL surge in a corresponding manner (for approximately 2 and 3 h, respectively). Thus, in addition to its PRL-releasing effects, TRH can also suppress the PRL secretion by stimulating the release of DA from TIDA neurons, thereby increasing the inhibitor DAergic tone on lactotrophs. During the interphase, when DA levels were relatively elevated, administration of the DA blocking agent HA 966 (100 mg/kg body weight i.p.) at 20.00 h resulted in a short-lasting decrease in extracellular DA levels (to approximately 60% of pretreatment values for 30 min) accompanied by an immediate, short-lasting increase in PRL levels (to 400 ng/ml for approximately 1 h). Administration of CG 3703 (500 micrograms/animal i.v.) in combination with HA 966 (100 mg/kg body weight i.p.) at 20.00 h prevented the decrease in DA levels and the rise in plasma PRL values. Thus, the TRH analogue and HA 966 counteracted each other regarding the DAergic system, which again illustrates the stimulatory effect of the TRH analogue on the release of DA from TIDA neurons. Moreover, our results suggest that the interphase and the phase during which the nocturnal PRL surge occurs under the condition of PSP differ with regard to the DAergic inhibition of the PRL secretion; during the interphase the DAergic inhibitory tone prevents the rise in PRL secretion, while during the nocturnal PRL surge period another factor in addition to a decrease in DA levels appears necessary to increase plasma PRL levels.

Inducible expression of cellular retinoic acid-binding protein II in rat ovary: gonadotropin regulation during luteal development.

Two members of the superfamily of small intracellular carrier proteins for lipophilic compounds are cellular retinoic acid-binding protein and cellular retinoic acid-binding protein II [CRABP(II)]. CRABP is found in many adult tissues, whereas CRABP(II) is more restricted and is reported as abundant primarily in skin. Here we report a much greater expression of CRABP(II) in rat corpus luteum than in any other organ/tissue examined, including skin. A rat complementary DNA clone encoding CRABP(II) was isolated and the ovarian expression followed during gonadotropin induction of follicular development in the pseudopregnant rat. The pattern of rat CRABP(II) messenger RNA and protein expression correlated with the appearance of corpora lutea and the rise in progesterone production as the corpora lutea developed, and was similar to the induction of 3 beta-hydroxysteroid dehydrogenase. Immunohistochemical localization revealed that CRABP(II) appeared in luteal cells and was dramatically restricted to their cytoplasmic compartment, with no apparent presence in the nucleus. This suggests that CRABP(II) may be expressed to restrict retinoic acid from occupying nuclear retinoic acid receptors, implying that the differentiation and maintenance of the rat corpus luteum may involve in part a release of certain pathways from retinoid suppression.

Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats.

The ability of progesterone to reduce the cerebral edema associated with traumatic brain damage first became apparent when we observed that males had significantly more edema than females after cortical contusion. In addition, edema was almost absent in pseudopregnant female rats, a condition in which progesterone levels are high relative to estrogen. Progesterone injections given after injury also reduced edema and were equally effective in both males and females. The present experiment was done to determine if the progesterone-induced reduction in edema could also prevent secondary neuronal degeneration and reduce the behavioral impairments that accompany contusion of the medial frontal cortex. Progesterone-treated rats were less impaired on a Morris water maze spatial navigation task than rats treated with the oil vehicle. Progesterone-treated rats also showed less neuronal degeneration 21 days after injury in the medial dorsal thalamic nucleus, a structure that has reciprocal connections with the contused area.

Induction of enkephalin in tuberoinfundibular dopaminergic neurons of pregnant, pseudopregnant, lactating and aged female rats.

The tuberoinfundibular dopaminergic (TIDA) neurons projecting to the external zone of the median eminence arise in the dorsomedial and ventrolateral subdivisions of the arcuate nucleus. In cycling female rats these regoins contain only scattered enkephalin-immunoreactive (ENK-i) neurons some of which coexpress dopamine, detected by immunostaining for tyrosine hydroxylase (TH). The present immunocytochemical, in situ hybridization and retrograde-labeling studies show that each TIDA neuron of pregnant, pseudopregnant, lactating, and aged female rats contains ENK-like immunoreactivity and pro-ENK mRNA and projects to the hypophysial portal circulation. Ovariectomy of lactating and aged rats did not change ENK staining within TIDA neurons, suggesting that ovarian steroids do not play a critical role in the colocalization of ENK and dopamine. Since prolactin levels are elevated in each of these experimental animals, a possible role for prolactin in the induction of the ENK gene in TIDA neurons is suggested. Prolactin stimulates dopamine and its own secretion via a short-loop feedback mechanism. The sensitivity of this regulatory mechanism is altered in these experimental animals, resulting in elevated prolactin secretion. ENK, which has prolactin-releasing activity and is colocalized with dopamine, could mediate the positive short-loop feedback regulation and sustain elevated levels of prolactin in pregnant, pseudopregnant, lactating, and aged animals.