Plasma 17beta-estradiol Levels Research Articles

Identification of gnrh2 and gnrh3 and their expression during brood pouch growth and short-term benzo(a)pyrene exposure in lined seahorse (Hippocampus erectus)

Gonadotropin-releasing hormones (GnRH) regulate gonadal growth of teleosts. Benzo(a)pyrene (BaP) functions as a reproductive endocrine disruptor. Furthermore, endocrine regulation on brood pouch growth of Syngnathidaes is elusive. To better understand the role of GnRH in brood pouch growth and effects of BaP on reproductive endocrine in lined seahorse (Hippocampus erectus), gnrh2 and gnrh3 genes were identified. Results showed that lined seahorse GnRH2 and GnRH3 precursors included the conservative tripartite structure and their transcripts highly expressed in brain as other teleosts. Expression profiles of gnrh2 and gnrh3 transcripts were detected during brood pouch growth. Results indicated that brain gnrh2 transcripts remarkably increased at the middle-stage and late-stage of brood pouch growth, while brain gnrh3 transcripts significantly raised at the early-stage and middle-stage. These suggested that GnRH2 and GnRH3 regulated brood pouch growth at different stages. Short-term BaP exposure in lined seahorse was performed. Transcripts of gnrh2 and gnrh3 remarkably increased in females and males exposed to BaP. Besides, plasma 17-beta estradiol (E2) levels presented a reduced trend during female fish exposed to BaP. This revealed that BaP functioned as anti-estrogenic effects and it may result in high expression of gnrh mRNA. However, plasma 11-ketone testosterone (11-KT) levels showed an increased trend during male fish exposed to BaP. Taken together, these indicated interesting results of BaP on reproduction in each sex of seahorse. These observations contribute to provide novel information of regulation on brood pouch growth and effects of BaP on reproductive endocrine in Syngnathidaes.

Plasma 17beta-estradiol and alkali-labile phosphoprotein levels in male and female Tench (Tinca tinca) in the Anzali and Amirkolayeh wetlands

Environmental pollutants are potentiate to disturb biological processes such as metabolism, growth and reproduction of aquatic organisms. These compounds are able to cause gonadal abnormalities, biased sex ratios and alteration in reproductive physiology in fish. The aim of this study was to examine plasma 17β-estradiol (E2) and alkali-labile phosphoprotein (ALP) levels in male and female Tench ( Tinca tinca ) from a polluted (the Anzali Wetland) and a non-polluted environments (the Amirkolayeh Wetland). Samples were collected over the maturation season of Tench between May and June 2017. The results revealed significant difference in mean ALP and E2 between genders in the polluted environment. However, the mean plasma ALP concentrations in male Tench of the polluted environment (39.46±1.02 µg/ml) was 45% of the average recorded in female (86.18±2.25 µg/ml) and was two times higher than the amount measured in males in the non-polluted environment (18.68±0.35 µg/ml). High concentrations of E2, were detected in the male samples from the Anzali Wetland. Mean plasma E2 concentrations for male in the Anzali Wetland was almost two times higher than male in the Amirkolayeh Wetland. The results indicate that the reproductive physiology of Tench was affected by contaminants found in the Anzali Wetland, a highly polluted area.

Effect of photoperiod on endocrine profiles and vitellogenin expression in European eels Anguilla anguilla during artificially induced ovarian development

The aim of this work was to determine the effects of dark and light conditions on the E2, testosterone and thyroid hormones levels and on the gene expression levels (vitellogenin 1, vitellogenin 2, and estradiol receptor one) in European eels (Anguilla anguilla) during ovarian development induced by increasing doses of carp pituitary extracts (CPEs). The subjects were divided into 2 groups: 14-hour light:10-hour dark (Light Group) and 24-hour darkness (Dark Group). All the eels received intramuscular injections with CPE at a dosage of 10 mg/kg body weight (BW) once a week for the first 3 weeks, 20 mg/kg BW fourth-sixth week, 30 mg/kg BW seventh-ninth week, and 40 mg/kg up to the end of the experiment (13th week). Vitellogenin and estradiol receptor expression levels did not show significant differences between the two housing conditions whereas in both groups vitellogenin mRNA increased starting from first CPE injection. Testosterone and 17-beta estradiol plasma levels were significantly greater in the Dark Group compared with the Light Group starting from the ninth and the 13th week, respectively. These results suggest that darkness could be a useful variable for standardizing gonadal maturation in eels kept in captivity.

Progesterone Withdrawal, and Not Increased Circulating Relaxin, Mediates the Decrease in Myometrial Relaxin Receptor (RXFP1) Expression in Late Gestation in Rats1

In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7, 16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels were increased in RU486-treated animals compared with controls. RU486 treatment also caused significant increases in myometrial Esr1 and Vegf and a decrease in Esr2. MCA1 was administered i.v. to rats from GD 17 to GD 19. On GD 20, no significant effect of MCA1 treatment on myometrial RXFP1 expression was observed compared with controls. Furthermore, there was no change in Esr1 or Esr2. A significant reduction in myometrial Vegf, however, was observed. We suggest that blocking progesterone action with RU486 increases plasma 17beta-estradiol and myometrial Esr1 and results in decreased RXFP1 expression. In summary, myometrial RXFP1 expression is mediated mainly by progesterone and not circulating relaxin in pregnant rats.

Effects of pulp and paper mill effluent extractives on aromatase CYP19a gene expression and sex steroid levels in juvenile triploid rainbow trout

We evaluated plasma testosterone (T) and 17beta-estradiol (E2) levels and ovarian aromatase CYP19a gene expression following a single intraperitoneal injection of Chilean pulp and paper mill effluent extracts into juvenile triploid rainbow trout. Fish injected with untreated effluent extracts had increased plasma T after 4 days, while plasma E2 concentration was increased in fish injected with both primary and secondary treated effluent extracts at the same sampling period. Ovarian CYP19a gene expression as measured by qRT-PCR was significantly induced in fish injected with the untreated, primary and secondary treated pulp and paper mill effluent extracts. Similar induction of CYP19a expression was found in fish injected with the androgens androstenedione (ADD) and T. A Principal Component Analysis (PCA) was conducted in order to identify structure in relationships between all measured variables and identifying which factors were most responsible for the variance observed within the plasma steroid levels, upregulation of ovarian CYP19a gene expression and the final estrogenic effect of increased plasma VTG levels. This analysis indicated a cluster correlation between plasma T levels and CYP19a gene expression (Factor 1, explaining 27.2% of total variance), a cluster including condition factor and liver somatic index (Factor 2, explaining 17.3%) and an additional cluster including plasma E2 and vitellogenin levels (Factor 3, explaining an additional 15.8%). The present results indicate that Chilean pulp and paper mill effluent extracts cause estrogenic effects in triploid rainbow trout. These effects could be related to the compounds present in the effluent that act as estrogen receptor agonists, or that induce changes leading to increased amounts of endogenous estrogens, reflected by increased E2 levels and induced aromatase expression/activity.

The Amphibian (Rana esculenta) Brain Progesterone Receptor: Relationship to Plasma Steroids and Vitellogenic Cycle during the Gonadal Recovery Phase

We report the presence of a progesterone receptor (PR) in the brain of the female amphibian Rana esculenta and changes in the levels of this PR during the gonadal recovery phase in relation to different circulating steroid levels and steroid treatment. The highest level of the PR in the nuclear brain extract corresponded to a low level of plasma progesterone and occurred when vitellogenin synthesis was at a minimum. The lowest level was found during follicular growth, concomitant with increased plasma 17beta-estradiol and progesterone levels. The PR levels were significantly higher in ovariectomized female R. esculenta than in intact and sham-operated female frogs. Treatment with 17beta-estradiol and progesterone downregulated the frog brain PR, indicating that a possible progesterone-receptor interaction is involved in the modulation of vitellogenin.

Effects of Leuprolide Acetate on Selected Blood and Fecal Sex Hormones in Hispaniolan Amazon Parrots (Amazona ventralis)

The luteinizing hormone-releasing hormone agonist leuprolide acetate is used commonly to anage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plas a and fecal hormone levels in a psittacine species, a single 800 microg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17beta-estradiol and androstenedione levels and fecal 17beta-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17beta-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17beta-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17beta-estradiol, and fecal 17beta-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.

Increased blood pressure in mice lacking cytochrome P450 2J5

The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical functions, including metabolism of arachidonic acid and steroid hormones. Mouse CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic acids (EETs), modulate sodium transport and vascular tone. To define the physiological role of CYP2J5 in the kidney, knockout mice were generated using a conventional gene targeting approach. Cyp2j5 (-/-) mice develop normally and exhibit no overt renal pathology. While renal EET biosynthesis was apparently unaffected by the absence of CYP2J5, deficiency of this CYP in female mice was associated with increased blood pressure, enhanced proximal tubular transport rates, and exaggerated afferent arteriolar responses to angiotensin II and endothelin I. Interestingly, plasma 17beta-estradiol levels were reduced in female Cyp2j5 (-/-) mice and estrogen replacement restored blood pressure and vascular responsiveness to normal levels. There was no evidence of enhanced estrogen metabolism, or altered expression or activities of steroidogenic enzymes in female Cyp2j5 (-/-) mice, but their plasma levels of luteinizing hormone and follicle stimulating hormone were inappropriately low. Together, our findings illustrate a sex-specific role for CYP2J5 in regulation of blood pressure, proximal tubular transport, and afferent arteriolar responsiveness via an estrogen-dependent mechanism.

Sex differences in a transgenic rat model of Huntington's disease: decreased 17β-estradiol levels correlate with reduced numbers of DARPP32+ neurons in males

Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha- and beta-estrogen receptors and showed a correlation between cell numbers and 17beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD.

Gender determination in the Paiche or Pirarucu (Arapaima gigas) using plasma vitellogenin, 17β-estradiol, and 11-ketotestosterone levels

Arapaima gigas is an air-breathing giant fish of Amazonian rivers. Given its great economic and cultural importance, the aquaculture development of this species represents an evident solution to face the decline of wild populations. In captivity, reproduction occurs generally in large earthen ponds where stocks of a few tens of brooders are maintained together at the beginning of the rainy season (December-March in the Peruvian Amazon). Fry production relies on the spontaneous formation of male and female pairs, which build a nest, delimit a territory and guard the offspring for at least 20 days from other congeners and predators. However, as sex determination of A. gigas is not possible by morphological criteria, it is very difficult to optimize reproduction conditions and fry production in each pond, which seriously hampers the culture of this species. This situation prompted us to develop sexing methodologies based on (1) the detection of female specific plasma Vitellogenin (Vtg) using an enzyme immuno assay (EIA), and (2) the determination of plasma 17beta-estradiol and 11-ketotestosterone levels for immature specimens. The Vtg purification was performed by electro-elution after polyacrilamide gel electrophoresis (PAGE) from plasma of 17beta-estradiol treated A. gigas juveniles. Two different Vtg molecules were isolated, (Vtg(1) and Vtg(2)) with 184 and 112 kDa apparent molecular masses, respectively, and two antibodies were raised in rabbits for each Vtg molecule. Adult fish were 100% accurately sexed by Vtg EIA, while 100% of immature fish and 95% of adults were accurately sexed by 17beta-Estradiol and 11-Ketestosterone ratios. We also observed different color pattern development in male and female adult fish (6-year-olds) around the reproductive period.

Bioaccumulation of hexachlorocyclohexane, dichlorodiphenyltrichloroethane, and estradiol-17β in catfish and carp during the pre-monsoon season in India

This investigation was performed to monitor hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane (DDT, and its metabolites, refered to as DDTs), plasma levels of estradiol-17beta (E2), and the gonadosomatic index (GSI) between sampling sites of unpolluted ponds of Gujartal, Jaunpur (control site) and the polluted rivers Gomti (Jaunpur) and Ganga (Varanasi), which affect the reproductive physiology of some edible catfish and carp during the pre-monsoon season. HCHs and DDTs were measured by gas liquid chromatography (GLC) and hormones by radioimmunoassay (RIA). The results indicated that the level of HCHs and DDTs was very high in both the catfish and the carp captured from the polluted rivers compared with the fish captured from the control site. The GSI and E2 values were lower in both groups of fish when compared to the fish from the control site. The results also indicate that catfish showed greater bioaccumulation of HCHs and DDTs than carp, above the permissible limit, as compared to the fish from the control site. In conclusion, fish from the Gomti and Ganga rivers were highly polluted when compared with fish from the control site, as was evident from high levels of tissue bioaccumulation of HCHs and DDTs and decreased levels of plasma E2, inhibiting the reproductive physiology of these species at the receptor level. The levels exceeded the maximum residue limits (MRL) as recommended by Codex, hence it is suggested that the fish should be avoided for food purposes.

Precocious Puberty in a Girl with Floating-Harbor Syndrome

Floating-Harbor syndrome (FHS) is a rare genetic disorder characterized by short stature, delayed bone age, mild to moderate mental retardation, speech problems, and peculiar craniofacial features. In these patients pubertal development has been reported to be normal. In this paper, we describe a girl with FHS who developed precocious puberty. FHS diagnosis was made at 2 years 5 months on the basis of peculiar clinical features. At 7 years 7 months, the girl began pubertal development; her height was 112.5 cm (-2.42 SDS) and pubertal staging was B2 PH2 AH1. LHRH test underlined LH and FSH peak values of 11.7 mIU/ml and 6.2 mIU/ml, respectively. Plasma levels of 17beta-estradiol were normal (8.5 pg/ml). Ophthalmological and neurological examinations, including nuclear magnetic resonance imaging of the brain, were normal. Treatment with gonadotrophin-releasing hormone analogue was begun. At 10 years 1 month, because of reduced height velocity, her growth hormone secretion was evaluated with diagnosis of neurosecretory dysfunction; hGH therapy was begun. The patient showed a good response to hGH treatment, reaching a normal adult height (156.1 cm; -1.20 SDS). This report suggests that, in patients with FHS, precocious puberty should be taken into consideration; in these patients, a careful endocrinological followup for the possible presence of growth and pubertal disorders is needed.

Ovarian development and plasma sex steroid levels in cultured female Senegalese sole Solea senegalensis

Ovarian development was studied in cultured female Senegalese sole Solea senegalensis. Females with regressed ovaries, mainly occupied by perinucleolar oocytes, predominated throughout summer exhibiting low condition factor (K), gonadosomatic index (I(G)), and plasma 17beta-estradiol and testosterone levels. Throughout autumn and winter (ovaries at early and intermediate maturation), oocytes progressed to cortical alveoli and vitellogenic stages accompanied by increasing K, I(G), and plasma 17beta-estradiol and testosterone levels. At late winter/early spring, ovarian development reached its maximum with the predominance of females at intermediate and final maturation (the latter occupied by late vitellogenic oocytes and few early maturation oocytes) and peak values of K, I(G), and 17beta-estradiol and testosterone concentrations. Steroid levels were lower (especially testosterone) than those for naturally-spawning females, which might cause extensive atresia without final oocyte maturation (no spawning was observed). This degenerative process reduced de size of the ovary (initial and intermediate phases of regression) in association with declining K, I(G), and plasma 17beta-estradiol and testosterone levels and increasing proportions of perinucleolar oocytes. The circulating 17,20beta-dihydroxy-4-pregnen-3-one levels, the proposed maturation-inducing steroid, remained relatively constant throughout the experimental period, suggesting that oocytes were unable to respond adequately to its stimulation. We propose the inadequate seasonal thermal regime as the main cause of such dysfunction.

Annual changes in ovarian development and plasma estradiol-17beta level in reared female common Japanese conger, Conger myriaster

Annual changes in the gonadosomatic index (GSI), oocyte diameter, gonadal histology and plasma estradiol-17β (E2) levels were investigated in female common Japanese conger Conger myriaster in captivity. Juveniles were caught in September 1999 and reared in seawater at temperatures ranging from 10–20°C for 3 years. All fish were immature when captured in September 1999. GSI and oocyte diameter increased from October 2000, peaked between summer and autumn 2001, and bottomed-out in winter 2001. Plasma E2 level also increased from October 2000, but remained high. The ovarian developmental stage was at the peri-nucle olus stage or the oil droplet stage until September 2000. Vitellogenesis started in October 2000 and oocytes progressed to the tertiary yolk globule stage by summer 2001. However, vitellogenic oocytes regressed in all females after autumn 2001. The neogenetic oocytes began to increase after November 2001 and ovarian development progressed in 2002 as they did in 2001, although maximum GSI in 2002 was half its 2001 value. These data indicate that ovarian development in the common Japanese conger has an annual periodicity, and that these congers may be able to spawn in multiple years under rearing condition.

Reproductive Characteristics of Bufo bankorensis at Two Elevations in Taiwan

We compared the reproductive characteristics of two populations of Bufo bankorensis in central Taiwan, one inhabiting a temperate climate (Meifong, 2100 m), the other inhabiting a subtropical climate (Wushe, 1100 m). We determined ovary status, spermatogenetic activity, fat body and liver mass cycles, and plasma 17-betaestradiol and androgen levels over a 14 month period. B. bankorensis from both populations are prolonged breeders but the temperate population exhibits breeding activity throughout the year, while the subtropical population only breeds from September to March. Their spermatogenic cycles are continuous, and their spermatogenetic activities are invariably at stage 6, in which spermatozoa are predominant in the seminiferous tubule. Both populations show monthly variations in plasma androgen and 17-betaestradiol levels, but follow different patterns. Ovary mass is larger in the temperate than in the subtropical population. The reproduction differences of two elevation toads could be reflected by adaptations to the local environmental regimes of its habitat. The reproductive patterns of these populations of Bufo bankorensis are also compared to those of sympatric and allopatric populations of five anurans studied from sites throughout Taiwan.

The follicle-deplete mouse ovary produces androgen.

The follicle-depleted postmenopausal ovary is enriched in interstitial cells that produce androgens. This study was designed to cause follicle depletion in mice using the industrial chemical, 4-vinylcyclohexene diepoxide (VCD), and characterize the steroidogenic capacity of cells in the residual ovarian tissue. From a dose-finding study, the optimal daily concentration of VCD was determined to be 160 mg/kg. Female B6C3F(1) immature mice were treated daily with vehicle control or VCD (160 mg kg(-1) day(-1), 15 days, i.p.). Ovaries were removed and processed for histological evaluation. On Day 15 following onset of treatment, primordial follicles were depleted and primary follicles were reduced to about 10% of controls. On Day 46, primary follicles were depleted and secondary and antral follicles were reduced to 0.7% and 2.6% of control, respectively. Seventy-five percent of treated mice displayed disruptions in estrous cyclicity. All treated mice were in persistent diestrus (acyclic) by Day 58. Plasma FSH levels were increased (P < 0.05) relative to controls on Day 37 and had plateaued by Day 100. Relative to age-matched cyclic controls, by Day 127, the significant differences in VCD-treated mice included reduced ovarian and uterine weights, elevated plasma LH and FSH, and reduced plasma progesterone and androstenedione. Furthermore, plasma 17beta-estradiol levels were nondetectable. Unlike controls, immunostaining for LH receptor, and the high density lipoprotein receptor (SR-BI), was diffuse in ovarian sections from VCD-treated animals. Ovaries from Day 120 control and VCD-treated animals were dissociated and dispersed cells were placed in culture. Cultured cells from ovaries of VCD-treated animals produced less LH-stimulated progesterone than control cells. Androstenedione production was nondetectable in cells from cyclic control animals. Conversely, cells from VCD-treated animals produced androstenedione that was doubled in the presence of insulin and LH (1 and 3 ng/ml). Collectively, these data demonstrate that VCD-mediated follicle depletion results in residual ovarian tissue that may be analogous to the follicle-deplete postmenopausal ovary. This may serve as a useful animal model to examine the dynamics of follicle loss in women as ovarian senescence ensues.

Effects of physical training on body composition and organ weights in ovariectomized and hyperestrogenic rats.

To investigate whether regular endurance-type exercise can benefit rats submitted to a model of ovariectomy (OVX)-induced obesity with or without estrogen replacement. OVX Sprague-Dawley rats were compared to an ovariectomized-estradiol-treated group (OVXE2) and a Sham-operated (Sham) group. Each of these groups were subdivided into a sedentary and a treadmill-trained (8 wk) group. An experimental study in which various parameters, including fat depots, blood lipids and several organ weights were measured. Plasma levels of 17beta-estradiol and uterus weights were significantly (P<0.05) lower in OVX compared to Sham and significantly (P<0.01) higher in OVXE2 (hyperestrogenic) compared to Sham rats. Body weights were significantly (P<0.01) different among groups, in the following decreasing order: OVX, Sham and OVXE2. The average daily food intake and food efficiency were significantly (P<0.01) increased in OVX compared to Sham, whereas estradiol treatment diminished this effect (P<0.01). Exercise training did not alter any of the above-mentioned variables in any of the three estrogen groups. Mesenteric and subcutaneous fat weights were significantly (P<0.01) increased by OVX. This increase was abolished by estrogen replacement or by exercise training. Exercise training also decreased fat weights in OVXE2 and Sham rats. OVX resulted in a decrease in the weights of several other tissues (femur, heart, lungs, liver and adrenal glands) while hyperestrogenic replacement resulted in an increase in weight of all measured tissues. Aside from fat depots, exercise training did not affect any of the tissue weights with the exception for an increase in the weight of the plantaris muscle and adrenal glands and a decrease in lung weight in all three estrogen groups. In OVX animals, exercise training may bring about positive changes in body composition (ie reduction in fat weights) despite an ovariectomy-induced increase in body weight.

Regulation of follicle-stimulating hormone secretion by estradiol and dimeric inhibins in the infantile female rat.

Plasma and ovarian levels of the dimeric forms of inhibin and plasma estradiol-17beta were investigated and compared with changes in plasma gonadotropins from Postnatal Day (PND) 5 to PND 30 in the female rat. The inhibin subunit proteins were localized in follicular granulosa cells of the ovary. Plasma immunoreactive inhibin levels were low until PND 15 and increased thereafter. Plasma levels of inhibin B (alpha and beta(B) subunits) remained very low until PND 15 and then increased by approximately 24-fold. In contrast, plasma levels of inhibin A (alpha and beta(A) subunits) were relatively low and steady until PND 20, then increased by approximately 3-fold at PND 25. Changes in ovarian inhibin A and B levels closely resembled those in plasma levels. Plasma FSH levels were low at PND 10 but started to peak from PND 15 and remained high until PND 20, followed by a remarkable reduction at PNDs 25 and 30. This dramatic fall in FSH coincided with the rise of inhibin A. A significant inverse correlation was observed between plasma FSH and plasma inhibin A (r = -0.67, P < 0.0002), ovarian inhibin A (r = -0.48, P < 0.01), plasma inhibin B (r = -0.48, P < 0.05), and ovarian inhibin B (r = -0.54, P < 0.01). Plasma estradiol-17beta levels were elevated from PND 5 through PND 15, then fell sharply through PND 30. Plasma estradiol-17beta was significantly and positively (r = 0.75, P < 0.0002) correlated with plasma FSH. Plasma LH rose to higher levels at PND 15 and tended to be lower thereafter. The inhibin alpha, beta(A), and beta(B) subunits were localized to primary, secondary, and antral and large antral follicles, but the types of these immunopositive follicles varied with age. It appeared that, at PND 25 and afterward, all three subunits were mainly confined to large antral follicles in the ovary. We conclude that estradiol-17beta likely is the major candidate in stimulation of FSH secretion in the infantile female rat. We also conclude that inhibin regulation of pituitary FSH secretion through its negative feedback in the infantile female rat begins to operate after PND 20. We suggest that this negative feedback is achieved by increases in plasma levels of the two dimeric forms, and that inhibin A appears to be the major physiological regulator of FSH secretion at the initiation of this mechanism. We also conclude that large antral follicles in the ovary are the primary source of these bioactive inhibins that are secreted in large amounts into the circulation after PND 20.

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females.

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.

Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia. Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02). Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.