Subcutaneous Injections Of Progesterone Research Articles

The relationship between sex steroids (E2, progesterone, and AMH) levels and severity and fatality of COVID-19: A systematic review

Sex steroids are powerful modulators of the immune system and they may affect the immune response and inflammatory consequences of COVID-19. This systematic review aims to explore the impact of sex steroids on COVID-19 mortality and complications. We looked up the keywords of the study in Scopus, PubMed, and Web of Science. All related original articles published in English, as of October 16, 2021, were reviewed to be included in our research. Concerns regarding the effect of sex hormones on COVID-19, eight full texts have been identified for the conclusion. In these studies, the relationship between estradiol and COVID-19 mortality has been mentioned. The most significant findings were the higher COVID-19 mortality rate in men, compared to women; also, in menopausal women compared to younger women and who received estradiol. In two studies, oral contraceptive pills had a protective effect on the morbidity of SARS-CoV-2 infection. In a randomized controlled trial, subcutaneous injection of progesterone in hospitalized men significantly reduced their symptoms and need for oxygen therapy. Hormone replacement therapy was positively associated with reducing COVID-19 symptoms. Although the results were insufficient for a conclusion, this study represents estrogen as an appropriate pharmacological method for preventing and diminishing the inflammation related to COVID-19 disease. However, future prospective studies and clinical trials are needed to clarify and approve this protective effect.

O-241 Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study

Abstract Study question Do patients with high serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy (HRT) present worse reproductive outcomes? Summary answer Elevated serum progesterone levels before FET in artificially prepared cycles with vaginal or vaginal plus subcutaneous progesterone do not impair reproductive outcomes. What is known already Low serum progesterone levels before FET do negatively affect reproductive outcomes in terms of live birth rate. However, there is not robust data regarding the impact of high serum progesterone levels in the luteal phase of patients who undergo HRT for FET. Study design, size, duration Retrospective cohort study of 3183 blastocyst FET cycles under HRT performed in a university-affiliated fertility centre between March 2009 and December 2020. All the cycles presented adequate serum progesterone levels before FET (≥10.6 ng/ml). A total of 1360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1024 were euploid ET (eu-FET) after preimplantational genetic testing for aneuploidies (PGT-A), and 799 cycles were frozen heterologous ET (het-FET). The primary objective was live birth rate (LBR). Participants/materials, setting, methods Standard HRT was used. Luteal phase was covered with vaginal progesterone 200 mg/8h, or vaginal plus a daily subcutaneous injection of progesterone (25 mg). Serum progesterone levels were measured the day before FET. Elevated progesterone levels were considered in the 90th and 95th centiles. A generalized additive model (GAM) was performed to study the functional relationships between progesterone and LBR. A multivariable logistic regression was used to evaluate the effect of high progesterone over LBR. Main results and the role of chance Mean serum progesterone level before FET was 16.77±8.43 ng/ml. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (21.87±14.17 vs. 15.56±5.72, p < 0.001). No differences in clinical pregnancy, miscarriage and LBR were found according to the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90, ≥22.33 ng/ml) and the rest of patients (p < 90) (43.9 vs 41.3%; p = 0.381). Patients with progesterone levels ≥p90 presented lower BMI compared to those in the lower centiles (<p90) (22.62±3.82 vs. 23.32±4.06; P = 0.009). After dividing patients in deciles according to serum progesterone levels before, no differences in LBR were observed among groups (P = 0.938). No association was observed with GAM model between progesterone levels and LBR. A multivariable logistic regression adjusted by oocyte age, type of treatment and number of embryos transferred was applied for centile 90 and centile 95 of progesterone, and showed that serum progesterone in their highest levels did not negatively impact LBR. Limitations, reasons for caution The main limitation of this study is its retrospective design. The results only apply for patients under HRT with vaginal micronized progesterone alone or plus subcutaneous progesterone. Progesterone determination was measured before blastocyst FET. Extrapolation to other HRT protocols or timings of progesterone measurement needs to be validated. Wider implications of the findings The results of this study suggest that once a threshold of serum progesterone before FET is achieved, progesterone levels are not predictive of the clinical outcome. Actually, LBR are not negatively affected when progesterone levels are found in their highest centiles after luteal phase rescue with vaginal plus subcutaneous progesterone. Trial registration number Not applicable

Subcutaneous progesterone (Prolutex) versus vaginal (Cyclogest) for luteal phase support in IVF/ICSI cycles: a randomized controlled clinical trial

BackgroundTo compare the safety, efficacy, and tolerability of subcutaneous vaginal progesterone suppository for luteal phase support (LPS) in assisted reproduction technology (ART) cycles in patients referred to the Royan Institute.MethodsThis randomized clinical trial was conducted from August 2016 to March 2018. The infertile patients undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were evaluated. The controlled ovarian stimulation (COH) was performed in all of the patients with standard long GnRH agonist protocol. After ovum pickup, eligible women were randomly allocated into two groups. In group A, since oocyte retrieval day, subcutaneous injections of progesterone (50 mg) (Prolutex®) were used daily, and in group B, two vaginal suppositories (Cyclogest ®) were administrated for LPS. The clinical pregnancy and miscarriage rates and the drug’s side effect were compared between two groups by appropriate statistical tests.ResultsFinally, 40 patients in each group were enrolled, and the IVF/ICSI outcomes were compared between groups. The data analysis showed that no significant differences were found between groups in terms of the demographic, infertility characteristics, and the COH outcome between groups. The chemical and clinical pregnancy rates (CPR) in group A were significantly higher than those of group B (P = 0.04, P = 0.02, respectively). The implantation and twin pregnancy rates in group B were significantly higher than those in group A (P = 0.009, P = 0.02, respectively).ConclusionThe subcutaneous administration of progesterone 25 mg twice daily for LPS was associated with higher CPR versus vaginal progesterone, and it was safe and well-tolerated in the follow-up. In addition, it can be a suitable replacement in cases of allergic reactions to vaginal suppositories. However, further study is required to compare the cost-effectiveness of these medications.Trial registrationThe study was also registered in the Iranian Registry of Clinical Trials on February 19, 2015 (IRCT201402191141N18 at www.irct.ir, registered prospectively).

Prophylactic progesterone prevents adverse behavioural and neurocognitive effects of neonatal anaesthesia exposure in rat

BackgroundEvidence from animal models and human studies suggests an association between early general anaesthesia exposure and development of long-lasting neurocognitive problems including learning and memory impairments and an anxious phenotype. Because millions of children each year undergo procedures that require anaesthesia, it is important to investigate ways to protect the vulnerable developing brain. We evaluated whether progesterone treatment administered before general anaesthesia exposure could prevent long-term anaesthesia-induced neurocognitive and behavioural changes. MethodsFemale and male Long–Evans rat pups were repeatedly exposed to 2 h of sevoflurane or control procedures at postnatal days 7, 10, and 13. Subcutaneous injections of progesterone or vehicle were administered immediately before general anaesthesia exposure or control procedures. Neurobehavioural and cognitive outcomes were evaluated using elevated plus maze and Morris water maze tests. ResultsProphylactic progesterone treatment attenuated the chemokine (C-X-C motif) ligand 1 (CXCL1) response to sevoflurane exposure. Rats given vehicle treatment with general anaesthesia exposure exhibited increased anxiety on the elevated plus maze and learning and memory impairments on the Morris water maze. However, rats treated with progesterone before general anaesthesia lacked these impairments and performed in a similar manner to controls on both tasks. ConclusionsProgesterone attenuated the anaesthesia-induced, acute peripheral inflammatory response and prevented cognitive and behavioural alterations associated with early repeated general anaesthesia exposure. Importantly, our results suggest that progesterone treatments given before general anaesthesia may help to protect the developing brain.

Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer's disease-like rats.

A correlation between metabolic alterations of neuroactive steroids and Alzheimer's disease remains unknown. In the present study, amyloid beta (Aβ) 25-35 (Aβ25-35) injected into the bilateral hippocampus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was significantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer's disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-α and interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-α and interleukin-1β in a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer's disease via neuroactive steroids, particularly progesterone.

Differential contribution of GABAergic and glycinergic components to inhibitory synaptic transmission in lamina II and laminae III–IV of the young rat spinal cord

Using whole-cell patch-clamp recordings from spinal cord slices of young (10-15 days old) rats, we have characterized and compared the properties of inhibitory synaptic transmission in lamina II and laminae III-IV of the dorsal horn, which are involved in the processing of nociceptive and non-nociceptive sensory information, respectively. All (100%) of laminae III-IV neurons, but only 55% of lamina II neurons, received both gamma-aminobutyric acid (GABA)ergic and glycinergic inputs. The remaining 45% of lamina II neurons received only GABAergic synapses. Neurons receiving only glycinergic synapses were never observed. Among the 55% of lamina II neurons receiving both GABAergic and glycinergic inputs, all displayed a small proportion (approximately 10%) of mixed miniature inhibitory postsynaptic currents (mIPSCs), indicating the presence of a functional GABA/glycine co-transmission at a subset of synapses. Such a co-transmission was never observed in laminae III-IV neurons. The presence of mixed mIPSCs and the differences in decay kinetics of GABAA-type receptor mIPSCs between lamina II and laminae III-IV were due to the endogenous tonic production of 3alpha5alpha-reduced steroids (3alpha5alpha-RS) in lamina II. Stimulation of the local production of 3alpha5alpha-RS was possible in laminae III-IV after incubation of slices with progesterone, subcutaneous injection of progesterone or induction of a peripheral inflammation. This led to the prolongation of GABAergic mIPSCs, but failed to induce the appearance of mixed mIPSCs in laminae III-IV. Our results indicate that, compared with lamina II, inhibitory synaptic transmission in laminae III-IV is characterized by a dominant role of glycinergic inhibition and the absence of a functional GABA/glycine co-transmission.

Differential expression and regulation of prostaglandin transporter and metabolic enzymes in mouse uterus during blastocyst implantation

To examine the spatiotemporal expression and regulation of prostaglandin transporter (PGT), 15-hydroxy-PG dehydrogenase (15-PGDH), and carbonyl reductase 1 (CBR1) messenger RNA (mRNA) and protein in the mouse uterus during embryo implantation and in related models. Experimental animal study. University research laboratory. Sexually mature female Kunming strain white mice. Delayed and activated implantation, artificial decidualization, and subcutaneous injection of progesterone (P) and E(2) in ovariectomized mouse. The expression of mRNA and protein were detected by in situ hybridization and immunohistochemistry in mouse uterus. Prostaglandin transporter mRNA and protein were expressed in the subluminal stroma at implantation site on day 5 of pregnancy and then in decidua but were not detected at the interimplantation sites and in preimplantation or pseudopregnant uterus. The presence of an active blastocyst was required for PGT expression at the implantation site. Both 15-PGDH and CBR1 mRNA were detected in glandular epithelium on day 4 of pregnancies. The expression of 15-PGDH and CBR1 mRNA was also detected in postimplantation embryos. These data suggest that differentially expressed PGT and 15-PGDH may participate in PG signaling in mouse uterus during implantation and decidualization.

Progesterone, but Not Progesterone-Independent Activation of Progestin Receptors by a Mating Stimulus, Rapidly Decreases Progestin Receptor Immunoreactivity in Female Rat Brain

Recent studies suggest that progestin receptors may be activated in vivo by neurotransmitters in the absence of ligand. More specifically, vaginal–cervical stimulation (VCS) can influence sexual behavior by activating progestin receptors in the absence of progesterone. Another way to test if progestin receptors are influenced by particular stimuli is to examine progestin receptor immunostaining. We report that progestin receptor immunoreactivity is decreased in the forebrain of estradiol-primed ovariectomized (OVX) rats within 1 h after a subcutaneous injection of progesterone, a time by which rapid down-regulation of progestin receptors does not seem to have occurred. In estradiol-primed OVX rats, VCS also decreased progestin receptor immunoreactivity within 1 h in the medial preoptic area, but not in any other area examined. To determine if the decrease in immunoreactivity by VCS was due to adrenal secretions or by ligand-independent activation of progestin receptors, we repeated the experiment in estradiol-primed OVX/adrenalectomized rats. Prior removal of the adrenal glands blocked the rapid decrease in progestin receptor immunoreactivity, even though data from other experiments suggest that progestin receptors are activated by VCS at this time. These studies suggest the possibility that progestin receptors may be affected differentially by progesterone-dependent or by progesterone-independent pathways. This raises the possibility that activation of progestin receptors by these two distinct pathways may lead to different neuronal consequences.

Progesterone regulates gamma-aminobutyric acid B (GABA B) receptors in the neocortex of female rats

After discovering that binding to GABA B receptors in rat neocortex varied as a function of the estrous cycle of the rat, we asked whether either or both of the major ovarian steroids could affect binding to GABA B receptors in the same way, namely, by regulating the apparent density ( B max) of GABA B receptors. We report here that in ovariectomized rats, subcutaneous injection of progesterone alone, without the necessity of estrogen priming, increased the Borax of baclofen binding to GABA B receptors in the neocortex. Radioimmunoassay of plasma progesterone before and after progesterone injections revealed that plasma progesterone levels similar to those reached during the progesterone surge in proestrus were associated with increased baclofen binding. The effect of progesterone upon baclofen binding was evident 4 h but not 1 h following progesterone treatment. There was some specificity with respect to the cortical receptors affected by progesterone in that under our conditions, progesterone did not increase agonist binding to 5-HT 1A or GABA A receptors. We interpret our results to indicate that progesterone variation during the estrous cycle could be responsible for a component of the regulation of GABA B receptors that occurs in neocortex during the estrous cycle of the rat.

Progesterone regulates gamma-aminobutyric acid B (GABAB) receptors in the neocortex of female rats

After discovering that binding to GABAB receptors in rat neocortex varied as a function of the estrous cycle of the rat, we asked whether either or both of the major ovarian steroids could affect binding to GABAB receptors in the same way, namely, by regulating the apparent density (Bmax) of GABAB receptors. We report here that in ovariectomized rats, subcutaneous injection of progesterone alone, without the necessity of estrogen priming, increased the Borax of baclofen binding to GABAB receptors in the neocortex. Radioimmunoassay of plasma progesterone before and after progesterone injections revealed that plasma progesterone levels similar to those reached during the progesterone surge in proestrus were associated with increased baclofen binding. The effect of progesterone upon baclofen binding was evident 4 h but not 1 h following progesterone treatment. There was some specificity with respect to the cortical receptors affected by progesterone in that under our conditions, progesterone did not increase agonist binding to 5-HT1A or GABAA receptors. We interpret our results to indicate that progesterone variation during the estrous cycle could be responsible for a component of the regulation of GABAB receptors that occurs in neocortex during the estrous cycle of the rat.

Progesterone releases dopamine in male and female rat striatum: A behavioral and microdialysis study

1. 1. The acute effect of progesterone at a physiological dose (50 μg) was investigated behaviorally by measuring postural deviation of rats bearing a unilateral lesion of the entopeduncular nucleus and biochemically by in vivo microdialysis in the striatum. 2. 2. Ovariectomized female and intact male rats displayed a significant increase of postural deviation to the lesioned side 30–65 min after the subcutaneous injection of progesterone with a return to control values thereafter. 3. 3. In addition, rats of both sexes had increased dopamine (DA) in the first 20–40 min dialysate collection following the progesterone injection. The metabolites of DA dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dialysate were also increased after the progesterone injection and HVA levels remained elevated for a longer time than DA, up to 120 min after progesterone. 4. 4. Progesterone, at a physiological dose and independently of estrogens can therefore rapidly increase DA release in the striatum of rats of both sexes as revealed in vivo behaviorally and biochemically.

Ovarian hormones influence odor stimulated flank marking behavior in the hamster (Mesocricetus auratus).

The effect of ovarian hormones on the frequency of female flank marking in response to the odors of male hamsters was examined. The amount of flank marking differed significantly (p less than 0.01) among the days of the estrous cycle, with the lowest levels of flank marking occurring on estrus. Ovariectomy (OVX) eliminated the 4 day rhythm, and significantly (p less than 0.01) reduced the total amount of flank marking. Implantation of Silastic capsules containing estradiol benzoate (EB) in OVX hamsters increased flank marking by approximately two-fold when compared to hamsters implanted with blank Silastic capsules. In a second series of experiments, OVX hamsters given EB flank marked significantly (p less than 0.01) more than those with blank capsules. Subcutaneous injection of progesterone (P) into OVX-EB treated hamsters 6 hr prior to testing significantly reduced flank marking when compared to OVX-EB treated hamsters given oil. No differences were observed in flank marking between groups of OVX hamsters with blank capsules and injected with P or oil. In summary, these data indicate that the four day rhythm of odor stimulated flank marking in intact female hamsters may be the result of the 4 day fluctuations of estrogen and progesterone that occur during the estrous cycle.

Interruption of Pregnancy in Rats by Azastene, an Inhibitor of Ovarian and Adrenal Steroidogenesis

Azastene (4,4,17alpha-trimethylandrost-5-eno[2,3-d]isoxazol-17-ol), when given orally to rats at a dose of 12 mg/kg once on day 10 of pregnancy, induced resorption of all fetuses and a precipitous decline of circulating progesterone levels in all test animals. The disruption of pregnancy was prevented by a single, concurrent, subcutaneous injection of progesterone (4 mg/rat). Thus, the interruption of pregnancy occurs via an acute, short-term, reversible progesterone withdrawal. The reduction of progesterone levels is brought about by competitive inhibition of ovarian 3beta-hydroxysteroid dehydrogenase activity. Despite its potency as an interceptive agent, azastene exhibited only moderate endocrine-related effects if given daily for 2 weeks to female rats at doses as high as 1000 mg/kg. Those effects were an increase in the number of vaginal estrous days and a dose-related increase in adrenal weight. The latter effect is consistent with the known adrenal inhibitory properties of this drug.

ADVANCEMENT OF OVULATION IN THE GUINEA-PIG WITH EXOGENOUS PROGESTERONE AND RELATED EFFECTS ON LENGTH OF THE OESTROUS CYCLE AND LIFE SPAN OF THE CORPUS LUTEUM

A single subcutaneous injection of progesterone (0-4 mg) was given to intact female guinea-pigs on either day 1, 7, 12, 13, 14, 15, or 16 of the behavioral oestrous cycle (day of oestrus is day 0). Injections given on either day 1 or day 7 had little effect, although there was a suggestion that injection on day 7 produced a lengthening of the cycle. Animals injected on either day 12 or day 13 underwent cycles of 16-9 and 18-1 days average length, respectively, which were significantly longer than the mean of 15-8 days for uninjected control females. Injection of progesterone on days 14, 15, or 16 was associated with one of three distinct sequelae: (1) simple prolongation of the cycle associated with a return to spontaneous oestrus 4--7 days later; (2) advancement of ovulation, formation of abnormal corpora lutea, and return to spontaneous oestrus 9--13 days later, and (3) return to spontaneous oestrus 14--16 days after the progesterone injection. These findings suggest that progesterone can cause the release of ovulatory amounts of gonadotropin following a period of endogenous oestrogen conditioning of the gonadotrophic system. If progesterone is administered before oestrogen conditioning is complete, then it inhibits or delays the conditioning process, and spontaneous oestrus and ovulation are postponed.

Advancement of Behavioral Estrus by Subcutaneous Injection of Progesterone in the Four-Day Cyclic Rat

Four-day cyclic female Sprague- Dawley rats were each injected once with 2 mg progesterone in 0.25 cc sesame oil, at some time between 1900 hr on diestrus II and 0300 hr on proestrus. The earliest time at which estrous behavior was detected was 0100 hr proestrus, 3–6 hr after injection and 15–18 hr prior to the onset of normal heat. The proportion of subjects responding was low in groups receiving an early injection (30 and 20 % with injection at 1900 and 2130 hr diestrus II, respectively), and increased sharply to 70% and above for all subsequent injection times (2200 and 2330 hr diestrus II, and 0030, 0100, 0130 and 0300 hi- proestrus). In addition to inducing an early heat, progesterone also tended to delay the normal heat at least 1 day, if the injection occurred at or before 0130 hr proestrus. It appears that estrogen priming can be complete 15–18 hr before heat normally begins. The onset of behavior can be advanced with progesterone injections, and is probably triggered by progesterone in the normal...

Mating behavior: facilitation in the female rat after cortical application of potassium chloride.

Mating behavior in ovariectomized female rats treated with estrogen can be greatly enhanced by subcutaneous injections of progesterone. Application of potassium chloride to the cortex of females previously treated with estrogen can also induce greatly increased sexual receptivity as indicated by the lordosis response. This facilitation of mating behavior by a treatment known to cause functional decortication suggests that mechanisms mediating female mating behavior are under tonic inhibition by an inhibitory system which involves the cerebral cortex.

DIFFERENTIAL CONTROL OF SEX HORMONE AND OXYTOCIN UPON EVOKED POTENTIALS IN THE HYPOTHALAMUS AND MIDBRAIN RETICULAR FORMATION

This experiment was undertaken to elucidate the concept that alterations of sex hormone and oxytocin in the systemic circulation exert remarkable influences upon the excitabilities of the multisynaptic pathways in the central nervous system. Observations were made on ovariectomized matured cats and rabbits with or without estrogen or progesterone treatment. The electrodes were permanently implanted into the brain and around the sciatic nerve and the dorsal root of the sacral segment, recording the evoked potentials in the hypothalamus, mesencephalic reticular formation (RF) and the medial lemniscus (ML) by electrical stimulation of the contralateral sciatic nerve, the dorsal root of the sacral segment, or by electrical stimulation of the hippocampus and amygdala. The results were as follows:1. During estrus induced by estrogen-progesterone priming of ovariectomized animals, the evoked potentials in the periventricular arcuate nucleus (ARC) and the RF to which single shock stimuli were delivered from the sciatic nerve were facilitated as compared with those during anestrus, while those in the same regions by stimulation of the dorsal root of the sacral segment were inhibited. In the non-estrogen primed, ovariectomized animals, a subcutaneous in jection of progesterone (5mg) evoked the opposite response in the ARC and the RF from that during estrus. Sacral stimulation increased the potential while stimulation of the sciatic nerve inhibited the potential.The hippocampally evoked potential in the ARC was inhibited in estrus, while facilitated after subcutaneous injection of progesterone (5mg). On the contrary, the amygdalarly evoked potential was facilitated during estrus, and inhibited after a subcutaneous injection of progesterone (5mg). On the basis of observations of the evoked potential and EEG pattern it was suggested that LH (0.3U.) had a facilitatory effect on the activity of the hippocampushypothalamus system and an inhibitory effect on that of the amygdala-hypothalamus system. The effect of FSH (100 I.U.) on these two systems was the complete reverse of the LH effect. Furthermore, it was noted that the RF responded to FSH independent of the hypothalamic response.2. The sacrally evoked potential in the ARC was facilitated after an intravenous in jection of oxytocin (0.3-0.4 I.U.) during estrus, and this was inhibited during the period of highly concentrated progesterone in the blood; the sciatically evoked potential in this region was inhibited after oxytocin administration at estrus, and facilitated after subcutaneous injection of progesterone (5mg).Many more facilitatory and inhibitory effects upon the evoked potential were observed in the RF than in the ML at the midbrain level by the peripheral afferent volley after intravenous injection of oxytocin, as well as during the period of anestrus and estrus.The facilitatory or inhibitory effect of the evoked potential in the ARC elicited by the afferent volley was noticeably depressed after lesion of the RF, while a lesion of the ML exerted only a slightly depressing effect upon the evoked potential recorded in the same area of the ARC.In short, it was observed that during estrogen dominance over progesterone, for example at estrus, the function of the RF was to facilitate transmission of somato-sensory afferent impulses to the higher center, and the inhibit viscerosensory afferent impulses. Conversely, if the influence of progesterone exceeded that of estrogen, for example during pregnancy, the activity of the RF was reversed; transmission of the peripheral somato-sensory afferent impulses to the higher center was inhibited while transmission of viscero-sensory afferent impulses was facilitated. When oxytocin increased in systemic circulation the evoked potentials are inverted in both circumstances.

Effects of oral administration of medroxyprogesterone acetate and ethinyl estradiol on the transportation and development of rabbit eggs.

Fifty-four rabbits in groups of 6 were subcutaneously injected with progesterone or fed medroxyprogesterone acetate (MPA) for 3 days either before or after artificial insemination and an ovulation-inducing injection of HCG. Feeding with progesterone (2 mg/rabbit/day) before or after ovulation, or by injection after ovulation, had no effect on the development of eggs when examined on day 6. Subcutaneous injection of progesterone or feeding with MPA at the same dose before ovulation, however, induced a complete degeneration of eggs. Oral administration of MPA before ovulation at doses less than 2 mg/rabbit/day for 3 days was progressively less effective. Fifty-six rabbits were fed ethinyl estradiol (EE) or MPA on various days before and/or after insemination, or with one compound before and the other after insemination. When examined on day 6, degeneration of eggs was observed whenever 0.05 mg/rabbit/day of EE was fed for 3 days after ovulation or MPA (2 mg/rabbit/day) for 3 days before ovulation. Although a single feeding with MPA on day - 1 (the day before insemination) and a single feeding with EE on day 1 were effective, a single feeding with MPA on day -1, a single feeding with EE on day 1, or 3 feedings with EE before ovulation and 3 injections of progesterone after ovulation, all produced less egg degeneration. Fifty-two rabbits were fed MPA before ovulation or with EE after ovulation. Although the majority of eggs were fertilized and normal when examined on day 2, the rate of recovery was slightly lower, and the eggs reached the uterus sooner than in the controls. Another 50 rabbits were fed MPA before and/or with EE after ovulation and were examined on days 2, 3 and 4. In these animals the recovery rate decreased as time elapsed, egg transport was speeded, and many eggs recovered at later times were neither at the expected stage of development nor developing normally. Finally, 1-day rabbit eggs were transferred into the ampullae of the fallopian tubes of estrous rabbits treated with MPA or EE. When examined at various times, the recovery rate was very low in the recipients treated with EE after transfer. Early entry of eggs into the uterus was observed in the control recipients, in those treated with MPA before transfer, and in those treated with EE after transfer. Retention of eggs in the tubes, however, was found in the recipients treated with MPA after transfer. It is concluded that endogenous or exogenous estrogen causes rapid egg transport from the tube to the uterus, while endogenous or exogenous progesterone counteracts the estrogenic effect and slows egg transport. Administration of progesterone before ovulation or of estrogen after ovulation speeds the transport of eggs and causes their degeneration or expulsion from the uterus. (Endocrinology79: 939, 1966)

Plasma and urinary metabolites of progesterone-4-C 14 administered orally or subcutaneously to rabbits

The fate of orally versus subcutaneously administered progesterone-4-C14 was studied in rabbits. During the first 6 hours after subcutaneous injection of labeled hormone, plasma radioactivity rose smoothly with free steroids accounting for 8–30% of the total. On the other hand, ingested radioprogesterone was rapidly absorbed and converted to conjugated metabolites which constituted more than 99% of the total plasma radioactivity. Fractionation and thin layer chromatography of hydrolyzed plasma extracts revealed at least 6 metabolites, the preponderant one corresponding to 5β-pregnane-3α,20α-diol (pregnanediol). More pregnanediol was present in plasma following oral administration rather than subcutaneous injection of progesterone. In contrast to these findings, route of administration of the radiohormone had no observable influence on the pattern of excretion products in the urine. Urinary metabolites were in general qualitatively similar to those found in plasma. However, urine also contained considerable alkali-extractable radioactivity which had no counterpart in plasma.

THE EFFECT OF OESTROGENS AND ANTI-OESTROGENS ON DECIDUOMA FORMATION IN THE RAT.

SUMMARY The maximum sensitivity to single subcutaneous injections of oestradiol or dimethylstilboestrol (DMS) occurred approximately 60 hr. after the induction of pseudopregnancy. Injection of the two compounds together at this time showed only an additive effect, suggesting that DMS was acting as a pro-oestrogen rather than as an anti-oestrogen. Single subcutaneous injections of progesterone were unable to reverse completely the inhibitory action of oestradiol; 17-ethyl-19-nortestosterone was more effective. Low doses of MER-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenylethanol) slightly reduced decidual growth while higher doses, which were oestrogenic, inhibited deciduoma formation and decidual growth. In combination with oestradiol low doses of MER-25 antagonized the inhibitory action of oestradiol.