Peripheral Estradiol Concentrations Research Articles

Post-hatch changes in the histological structure of the oviduct and associated 17β-estradiol profiles in guinea hens (Numida meleagris)

There are limited data available on the biology of guinea fowls. The objective of this study was to document post-hatch histological and stereological changes in the oviducts of 56 guinea hens and associated 17β-estradiol profiles until 32 weeks of age and to explore changes in the oviducal mucosal fold as an index of oviducal growth. Mucosal folds in all regions of the oviduct increased significantly ( P < 0.0001) from 4 to 28 weeks of age. Concentrations of plasma 17β-estradiol increased from 20 to 28 weeks of age, when it stabilized. Mucosal folds in the oviducts of sexually active hens were highest in the uterine region and lowest in the infundibular lip. Intercorrelations among 17β-estradiol concentration, height of mucosal folds, and oviducal weight were strong and positive in these birds. Most of the oviduct epithelium consisted of pseudostratified columnar ciliated epithelium. Both the height of oviducal folds and peripheral estradiol concentrations increased significantly from 20 to 28 weeks of age, which confirms the role of estradiol in oviducal growth in the avian species. The height of oviducal mucosal folds appears to be a good measure of oviducal growth.

Age-related changes in the gross anatomy of the reproductive organs, and associated steroid hormone profiles in male and female guinea fowls (Numida meleagris)

Owing to the paucity of information on the reproductive biology of guinea fowls, a study involving a total of 132 birds was conducted, and this documented the developmental changes in the gross anatomy of the reproductive organs of males and females from hatching until 32 weeks of age (WOA), and associated steroid hormone changes. Testicular anatomical biometric traits increased significantly (p < 0.0001) from 8 WOA, and stabilised between 16 and 20 WOA, while peripheral testosterone concentration peaked at 20 WOA. Correlations among all testicular biometric characteristics were strong and positive (p < 0.0001). Similarly peripheral testosterone concentrations strongly (p < 0.01) and positively correlated with all the testicular anatomical biometric traits. In the female guinea fowl, the ovary and oviduct were discernible and measurable at hatching. Significant (p < 0.0001) increases were seen in ovarian and relative ovarian weights, and oviducal weights and lengths between 24 and 28 WOA. Plasma 17β-oestradiol decreased gradually to a very minimum at 16 WOA, and then began to increase gradually until 28 WOA when it plateaued. Peripheral progesterone concentrations on the other hand increased gradually from 4 WOA and peaked at 12 WOA, and then fluctuated considerably thereafter. Correlations among ovarian/oviducal anatomical parameters were strong (p < 0.0001) and positive. Similarly, peripheral oestradiol concentrations strongly (p < 0.0001) and positively correlated with all ovarian/oviducal anatomical parameters. Testicular anatomical biometric traits stabilised between 16 and 20 WOA, coinciding with peak peripheral testosterone concentrations, while ovarian/oviducal parameters recorded huge increases between 24 and 28 WOA, and may be under the influence of oestradiol.

Effects of season on the reproductive organs and steroid hormone profiles in guinea hens (Numida meleagris)

The study documented gross anatomical and histological differences in the reproductive organs of 28 breeding and non-breeding female guinea fowls. Peripheral progesterone and 17β-oestradiol concentrations were also compared in breeding and non-breeding hens.In non-breeding females, all ovarian and oviducal gross anatomical features had significantly regressed. Histologically, some of the changes in a regressing oviduct include systematic changes in height and size of all epithelial cells in all regions of the duct, absence/sparse ciliation of portions of surface epithelium in the magnum, isthmian and uterine regions, general loss of cytoplasmic mass, reduction in size and degeneration of tubular glands. Mucosal folds in all regions of the oviduct except the infundibular lip were higher in breeding females.No difference was found between the two groups in plasma progesterone concentrations. Breeding females, however, had higher peripheral oestradiol concentrations than non-breeding females. About 2 h prior to oviposition, plasma oestradiol concentrations peaked at 2.4-fold (230 pg/ml) compared with baseline concentration and plasma progesterone concentrations by nearly 9-fold (5.29 ng/ml) of baseline.Significant regression and changes in the histological structure of the ovary and oviduct had occurred in non-breeding females, and lower peripheral oestrogen concentrations may be responsible for this phenomenon.

Compared to dinoprost tromethamine, cloprostenol sodium increased rates of estrus detection, conception and pregnancy in lactating dairy cows on a large commercial dairy

Using two PGF2α treatments 14 days apart as a way to enhance estrus detection rate following the 2nd treatment is a reproductive management tool that continues to be used on large dairy farms. In one study, in cows with a functional CL and a dominant follicle, treatment with cloprostenol vs. dinoprost resulted in greater peripheral estradiol concentrations. The objective of the present study was to determine if cloprostenol could enhance pregnancy rates of cows in a large dairy herd using a PGF2α program for 1st artificial insemination (AI). Lactating dairy cows (n = 4549) were randomly assigned to receive two treatments of either 500 μg cloprostenol or 25 mg dinoprost 14 days apart, with the 2nd treatment on the 1st day of the voluntary waiting period (57 DIM). Cows detected in estrus within 5 days after the 2nd treatment were inseminated. There was no effect of treatment on day of estrus detection, with 78% of cows inseminated on Days 3 or 4 following treatment. Cloprostenol increased (P < 0.01) estrus detection rates in 1st parity cows compared to dinoprost, 42.4 vs. 34.0%. In cows inseminated on Days 3 or 4 after treatment, cloprostenol increased (P = 0.05) conception rates compared to dinoprost, 38.3 vs. 34.4%. When treatments and parities were combined, conception rates increased (P < 0.02) with interval after treatment (27.0, 36.4, and 44.5% for Days 1 or 2, Days 3 or 4, and Day 5, respectively). Cloprostenol increased (P = 0.02) overall pregnancy rate compared to dinoprost, 14.4 vs. 12.2%. In summary, cloprostenol increased fertility in 1st parity cows inseminated on Days 3 or 4 following treatment and subsequently enhanced pregnancy rates of 1st parity lactating dairy cows compared to dinoprost. Fertility appeared greater in cows expected to have had a young antral ovarian follicle at treatment.

Ovarian estradiol modulates the stimulatory effect of ovulation-inducing factor (OIF) on pituitary LH secretion in llamas

This study was designed to: 1) characterize the effect of ovulation-inducing factor (OIF) on pituitary LH secretion in ovariectomized (OVX) llamas; and 2) determine the effect of OIF on LH secretion in OVX llamas pretreated with estradiol-17β (E-17β) or estradiol benzoate (EB). In Experiment 1, intact and OVX llamas (n = 5 or 6 per group) were assigned to a two by two factorial design: 1) Intact llamas treated with 1 mL of phosphate buffered saline (PBS); 2) Intact llamas treated with 1 mg of purified OIF; 3) OVX llamas treated with 1 mL of PBS; or 4) OVX llamas treated with 1 mg of purified OIF. In Experiment 2, intact and OVX llamas (n = 5 or 6 per group) were randomly assigned to the following groups: 1) Intact llamas treated with 1 mg of purified OIF; 2) OVX llamas treated with 1.0 mL of PBS; 3) OVX llamas treated with 1.0 mg of purified OIF; 4) OVX llamas primed with E-17β, followed by 1.0 mg of purified OIF. Experiment 3 was similar as described for Experiment 2, except that priming was done with EB. In Experiment 1, animal category by treatment and animal category by treatment by time interactions tended (P = 0.08) to affect LH concentration. The effect of OIF on LH released was partly restored (P < 0.05), to the values observed for the intact OIF-treated females, when OVX llamas were primed with E-17β or BE (Experiments 2 and 3). We concluded that peripheral estradiol concentrations in llamas partially modulates the effect of OIF on pituitary LH secretion; however, other ovarian factor(s) could also participate in this modulatory action.

Paternal responsiveness in biparental dwarf hamsters ( Phodopus campbelli) does not require estradiol

Males of the biparental hamster species Phodopus campbelli act as midwives and are responsive to an experimentally displaced pup. Males also have peripheral estradiol concentrations that are similar to conspecific females. Castration reduces peripheral estradiol, yet does not affect paternal responsiveness despite the known role of estradiol in maternal behavior. Synthesis of estradiol within the central nervous system, however, might not be affected by castration. Males received implants of osmotic pumps containing the aromatase inhibitor letrozole to reduce both peripheral and central estradiol concentrations. Though estradiol was effectively reduced, it had no effect on paternal responsiveness or reproductive success. Neither testosterone nor aggression directed towards an intruder was altered. Results support the emerging conclusion that estradiol is not required for the exceptional paternal behavior of male P. campbelli.

Characterization of 11β-Hydroxysteroid Dehydrogenase Activity in Testicular Tissue of Control and GnRH-Immunized Boars as a Possible Regulator of Spermatogenesis

Glucocorticoids are involved in the regulation of spermatogenesis in the boar testis by initiating apoptosis in early stages of germ cell development. Because cortisol activity is modulated by the 11beta-hydroxysteroid dehydrogenase system (11beta-HSD), the present study determined both 11beta-activating (reductive) and inactivating (oxidative) enzyme activities in testicular tissue preparations of control boars (n = 5), GnRH-immunized boars (n = 5), and immunized, estradiol-infused boars (n = 6) by radioenzyme assay based on the conversion of tritiated cortisol to cortisone in the presence of NAD+ (inactivation) or tritiated cortisone to cortisol in the presence of NADPH (activation). The presence of both isoforms, 11beta-HSD 1 and 11beta-HSD 2, was confirmed by RTPCR in testicular tissue of control boars. Additionally, cortisol, testosterone, estradiol, and LH were determined in blood plasma sampled twice before killing. Immunization led to a drop of LH from 4.3 +/- 0.3 pmol/L to 1.0 +/- 0.3 pmol/L (testosterone: 11.63 +/- 0.83 nmol/L vs. 0.28 +/- 0.07 nmol/L; 17beta-estradiol: 512.61 +/- 47.60 pmol/L vs. 77.05 +/- 14.00 pmol/L). Low 11beta-HSD reductive activity was found in boars (1 pmol steroid x min (-1) x mg (-1)). It decreased to trace amounts in immunized boars (0.07 pmol steroid x min (-1) x mg (-1)). Oxidative activity was found in boars with 10.19 +/- 2.28 pmol steroid x min (-1) x mg (-1) protein. Immunization led to a sharp decrease (0.08 +/- 0.03 pmol x min (-1) x mg (-1)). Infusion of 17beta-estradiol significantly elevated peripheral estradiol concentrations to 752.07 +/- 24.19 pmol/L which still is a physiological concentration in this species. The infusion led to a minimal reductive activity (0.04 pmol steroid x min (-1) x mg (-1)), but led to a 6-fold rise of the 11beta-HSD oxidative activity to 0.47 +/- 0.14 pmol x min (-1) x mg (-1) compared to immunized boars. It is concluded that the 11beta-HSD system is involved in the regulation of cortisol activity in the testis and thus in the regulation of spermatogenesis.

Follicular waves are associated with transient fluctuations in FSH but not oestradiol or inhibin-A concentrations in anoestrous ewes

AbstractThe aim was to examine statistically the changes among days in the numbers of follicles relative to the growth of large follicles to test the hypothesis that follicular development occurs in a wave-like fashion in anoestrous ewes. The relationships among the patterns of circulating concentrations of FSH, oestradiol and inhibin-A and the pattern of follicular growth as well as relationships among follicular fluid steroid and inhibin-A concentrations were also studied. The ovaries of 11 ewes were examined daily using transrectal ultrasonography for 14 days and blood samples were collected every 8 h for 9 days. Five ewes were ovariectomized on the last day of ultrasound scanning. One to three identified follicles (a cohort) emerged every 2 to 5 days (mean 2·9 (s.e. 0·2) days) in individual ewes. The numbers of 4 and 5 mm follicles were fewest (P &lt; 0·05) before and greatest (P &lt; 0·05) 1 day after cohort emergence. This change in the numbers of follicles indicates a wave-like pattern of follicular growth. FSH concentrations were greatest (P &lt; 0·05) on the day before wave emergence and lowest (P &lt; 0·05) on the day of wave emergence. Peripheral concentrations of oestradiol and inhibin-A did not fluctuate (P &gt; 0·05) in association with the emergence of follicular waves. The follicles that were collected at ovariectomy originated from one of three different waves. Oestradiol and inhibin-A concentrations in follicular fluid and the oestradiol-to-progesterone ratio were not different among the largest follicles of successive waves, when follicles were collected at the same time, indicating that new waves of follicles developed before the demise of old waves.In conclusion, waves of follicles emerged about every 3 days in anoestrous ewes (defined as significant changes in numbers of follicles) and were associated with fluctuations in FSH concentrations but not peripheral oestradiol or inhibin-A concentrations. New follicular waves also emerged in the presence of steroidogenically active (positive oestradiol-to-progesterone ratio), inhibin-A producing follicles from a previous wave suggesting that follicles do not exert functional dominance during the non-breeding season.

Effect of finadyne on oestradiol-induced ovarian oxytocin and uterine PGF2alpha secretory systems on day 15 after oestrus in ovarian autotransplanted ewes

This study was undertaken to determine whether induction of ovarian oxytocin after oestradiol treatment on day 15 after oestrus is mediated through prostaglandin secretion by blocking prostaglandin synthesis using finadyne, an inhibitor of the cyclo-oxygenase pathway. Nine ewes with ovarian autotransplants were assigned randomly to receive an i.m. injection of either oestradiol benzoate (50 microg) in peanut oil ( n= 5) or oestradiol benzoate plus finadyne (2.2 mg kg (-1)) ( n= 4) at 3 h intervals starting at the time of oestradiol injection. Blood samples were collected from the ovarian and contralateral jugular veins at 30 min intervals for 6 h before and at 15 min intervals for up to 9 h after the oestradiol and finadyne injections. The secretion rate of ovarian progesterone remained high in all ewes, thus indicating the presence of a functional corpus luteum. Peripheral oestradiol concentrations were significantly (P < 0.001) higher during the 9 h after oestradiol injection in both groups. None of the oestradiol-finadyne-treated ewes showed significant pulses in either ovarian oxytocin secretion or release of the prostaglandin F(2alpha) metabolite 13,14-dihydro-15-keto PGF(2alpha) (PGFM) after injections. In ewes treated with oestradiol only, at least one detectable pulse of ovarian oxytocin and jugular PGFM was observed with mean +/- SEM amplitude of 17.7 +/- 7.29 ng min (-1) and 237.18 +/- 43.13 pg ml (-1), respectively. The areas under the curve for ovarian oxytocin and jugular PGFM pulses were significantly increased after oestradiol treatment. These findings demonstrate that initiation of the arachidonic acid cascade is important for the secretion of oxytocin after oestrogen treatment.

Effect of finadyne on oestradiol-induced ovarian oxytocin and uterine PGF2alpha secretory systems on day 15 after oestrus in ovarian autotransplanted ewes.

This study was undertaken to determine whether induction of ovarian oxytocin after oestradiol treatment on day 15 after oestrus is mediated through prostaglandin secretion by blocking prostaglandin synthesis using finadyne, an inhibitor of the cyclo-oxygenase pathway. Nine ewes with ovarian autotransplants were assigned randomly to receive an i.m. injection of either oestradiol benzoate (50 microg) in peanut oil ( n= 5) or oestradiol benzoate plus finadyne (2.2 mg kg (-1)) ( n= 4) at 3 h intervals starting at the time of oestradiol injection. Blood samples were collected from the ovarian and contralateral jugular veins at 30 min intervals for 6 h before and at 15 min intervals for up to 9 h after the oestradiol and finadyne injections. The secretion rate of ovarian progesterone remained high in all ewes, thus indicating the presence of a functional corpus luteum. Peripheral oestradiol concentrations were significantly (P < 0.001) higher during the 9 h after oestradiol injection in both groups. None of the oestradiol-finadyne-treated ewes showed significant pulses in either ovarian oxytocin secretion or release of the prostaglandin F(2alpha) metabolite 13,14-dihydro-15-keto PGF(2alpha) (PGFM) after injections. In ewes treated with oestradiol only, at least one detectable pulse of ovarian oxytocin and jugular PGFM was observed with mean +/- SEM amplitude of 17.7 +/- 7.29 ng min (-1) and 237.18 +/- 43.13 pg ml (-1), respectively. The areas under the curve for ovarian oxytocin and jugular PGFM pulses were significantly increased after oestradiol treatment. These findings demonstrate that initiation of the arachidonic acid cascade is important for the secretion of oxytocin after oestrogen treatment.

Effect of administration of eCG to postpartum cows on folliculogenesis in the ovary ipsilateral to the previously gravid uterine horn and uterine involution

This study tested the hypothesis that increased oestradiol secretion by large follicles in the ovary ipsilateral to the previously gravid uterine horn has a local effect to increase the rate of uterine involution. Cows were administered an i.m. water placebo (n = 19), 250 iu equine chorionic gonadotrophin (eCG) (n = 18) or 750 iu eCG (n = 20) 14 days post partum (day 0). Transrectal ultrasonography at the time of treatment and 2, 4 and 6 days later monitored uterine horn diameter and ovarian structures. Blood samples collected contemporaneously were assayed for 15-keto-13, 14-dihydro-prostaglandin F(2alpha) and oestradiol concentration. For control cows, accumulated diameter of the largest follicle in the ovary ipsilateral to the previously gravid uterine horn, compared with the contralateral ovary, was smaller on day 0 (P < 0.05) and days 2, 4 and 6 (P < 0.001). There were no significant differences in the eCG-treated animals. There were 12, 8 and 11 cows with a plasma oestradiol concentration < 1 pg ml(-1) on day 0 in the control, 250 and 750 iu eCG treatment groups, respectively. For control cows, the peripheral oestradiol concentrations were higher on day 6 compared with days 0, 2 and 4 (P < 0.05); for cows treated with 250 iu eCG, concentrations were higher on days 4 and 6 compared with day 0 (P < 0.05); and for cows treated with 750 iu eCG, concentrations were higher on days 2 and 4 compared with day 0 (P < 0.01). Treatment with eCG, or the presence of a follicle > 8 mm in diameter in the ovary ipsilateral to the previously gravid uterine horn, did not affect the rate of uterine involution or plasma 15-keto-13,14-dihydro-prostaglandin F(2alpha) concentration. In conclusion, administration of eCG to increase follicular growth and oestradiol production overcame the inhibition of follicular growth in the ovary ipsilateral to the previously gravid uterine horn, but did not affect uterine involution.

Effect of administration of eCG to postpartum cows on folliculogenesis in the ovary ipsilateral to the previously gravid uterine horn and uterine involution

This study tested the hypothesis that increased oestradiol secretion by large follicles in the ovary ipsilateral to the previously gravid uterine horn has a local effect to increase the rate of uterine involution. Cows were administered an i.m. water placebo (n = 19), 250 iu equine chorionic gonadotrophin (eCG) (n = 18) or 750 iu eCG (n = 20) 14 days post partum (day 0). Transrectal ultrasonography at the time of treatment and 2, 4 and 6 days later monitored uterine horn diameter and ovarian structures. Blood samples collected contemporaneously were assayed for 15-keto-13, 14-dihydro-prostaglandin F(2alpha) and oestradiol concentration. For control cows, accumulated diameter of the largest follicle in the ovary ipsilateral to the previously gravid uterine horn, compared with the contralateral ovary, was smaller on day 0 (P &lt; 0.05) and days 2, 4 and 6 (P &lt; 0.001). There were no significant differences in the eCG-treated animals. There were 12, 8 and 11 cows with a plasma oestradiol concentration &lt; 1 pg ml(-1) on day 0 in the control, 250 and 750 iu eCG treatment groups, respectively. For control cows, the peripheral oestradiol concentrations were higher on day 6 compared with days 0, 2 and 4 (P &lt; 0.05); for cows treated with 250 iu eCG, concentrations were higher on days 4 and 6 compared with day 0 (P &lt; 0.05); and for cows treated with 750 iu eCG, concentrations were higher on days 2 and 4 compared with day 0 (P &lt; 0.01). Treatment with eCG, or the presence of a follicle &gt; 8 mm in diameter in the ovary ipsilateral to the previously gravid uterine horn, did not affect the rate of uterine involution or plasma 15-keto-13,14-dihydro-prostaglandin F(2alpha) concentration. In conclusion, administration of eCG to increase follicular growth and oestradiol production overcame the inhibition of follicular growth in the ovary ipsilateral to the previously gravid uterine horn, but did not affect uterine involution.

Effect of oestradiol on ovarian oxytocin secretion rate and luteolysis in the ewe after ovarian auto-transplantation.

The release of ovarian oxytocin and uterine prostaglandin (PG)F2alpha in response to an oestradiol stimulus was investigated. On Day 15 post-oestrus, ten ewes with ovarian auto-transplants (n=5 per group) received an intra-muscular injection of either oestradiol benzoate (50 microg) or vehicle. Blood samples were collected from the ovarian and jugular veins at 30 and 0 min before, and at 15-min intervals up to 540 min after, injection. The secretion rate of ovarian progesterone remained elevated in four of five treated ewes and in all control ewes, indicating the presence of a functional corpus luteum. Peripheral oestradiol concentrations were significantly (P < 0.001) higher in treated than in control ewes. The number of ewes that released pulses of ovarian oxytocin > or =240 min following oestradiol benzoate injection was significantly (P < 0 05) greater than that in control ewes. Mean amplitude and area under both ovarian-vein oxytocin and jugular-vein 15 keto-13,14 dihydro prostaglandin F2alpha (PGFM) pulses were significantly increased in the treated ewes. These findings demonstrate that the administration of exogenous oestrogen provides a positive stimulus for the release of ovarian oxytocin and uterine PGF2alpha in the ovarian auto-transplanted ewe.

Developmental increase in placental low density lipoprotein uptake during baboon pregnancy.

The present study determined whether a developmental increase in placental low density lipoprotein (LDL) uptake occurred in baboon pregnancy, which was related to the increasing concentrations of estrogen typical of advancing gestation. LDL uptake was determined on collagenase-dispersed placental trophoblast cells purified via 50% Percoll gradient centrifugation and obtained from baboons between days 55-178 of gestation (i.e. the last two-thirds of gestation; term = 184 days). The majority of cells in the 50% Percoll-isolated fraction used to determine LDL uptake were syncytiotrophoblasts at all stages of gestation examined, as determined by immunohistochemical staining for syncytiotrophoblast-specific placental lactogen and pregnancy-specific-beta 1-glycoprotein. Placental LDL uptake, as determined by Scatchard analysis, increased progressively during the last two-thirds of gestation and was correlated (r = 0.87, P less than 0.001; curvilinear regression) with gestational age. Mean +/- SE LDL uptake early in pregnancy on days 55-58 was 1.9 +/- 0.2 ng/micrograms cell protein (n = 3). Placental LDL uptake (ng/microgram cell protein) at midgestation on days 94-104 (2.8 +/- 0.2; n = 5) increased to a value late in gestation on days 159-178 (14.6 +/- 1.0; n = 13), which was approximately 5-fold greater (P less than 0.001) than at midgestation, whereas uptake on days 128-138 was intermediate in value (8.3; n = 2) between the latter two periods. The apparent dissociation constant for placental LDL uptake was lower (P less than 0.01) at midgestation (0.33 micrograms/ml) than late in gestation (0.81 micrograms/ml). Placental LDL degradation, which depends on uptake, also increased with advancing stages of pregnancy, and was correlated (r = 0.74, P less than 0.01; curvilinear regression) with gestational age. Overall mean peripheral serum LDL cholesterol concentration was 46.5 +/- 1.7 mg/dl between days 50-170 of gestation. However, there was no significant change in serum LDL levels during this period. Maternal peripheral serum estradiol concentrations increased from 0.3 ng/ml on day 55 to an initial peak of approximately 3.5 ng/ml on days 70-80, then declined to approximately 1.0 ng/ml at midgestation. Estradiol then increased progressively throughout the remainder of pregnancy to maximal values of over 6 ng/ml late in gestation. In summary, there was a progressive increase in placental LDL uptake with advancing stages in the last two-thirds of baboon pregnancy, which was associated with a concomitant rise in maternal serum estradiol concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Forebrain sites of estradiol-17 beta action on sexual behavior and aggression in female Syrian hamsters.

The effects of intracranial implants of estradiol in the ventromedial hypothalamus (VMH), the anterior hypothalamus (AH), or the medial amygdala (AMG) on aggression, sexual behavior, and serum estradiol were examined in female Syrian hamsters. Estradiol implants in the VMH, followed by systemic progesterone, stimulated sexual behavior and inhibited aggression. Estradiol implants in other intracranial sites activated sexual behavior but did not reliably inhibit aggression. Intracranially implanted and systemically treated animals had equivalent peripheral estradiol concentrations at sacrifice. These results suggest that: (a) the VMH is an important neural site for estradiol actions on sexual and aggressive behavior, (b) the caudal AH and AMG also may be sites of estradiol action on sexual behavior, and (c) these intracranial implants may only be effective given systemic estradiol exposure or the concurrent stimulation of multiple brain areas.

Stimulation of progesterone secretion by cultured human granulosa cells with melatonin and catecholamines.

Granulosa cells, aspirated from the follicles of patients undergoing treatment for in-vitro fertilization, were cultured in serum-supplemented medium. Adrenaline and noradrenaline stimulated a dose-related increase in progesterone secretion with a maximum stimulation at 10(-5) M, a response that was prevented by the beta-antagonist, propranolol. Adrenaline and hCG showed similar characteristics in their stimulation of progesterone secretion but there was no further increase in progesterone when the 2 compounds were added together. Melatonin stimulated progesterone secretion and, like adrenaline, this stimulation was prevented by propranolol. The ability of both adrenaline and melatonin to increase progesterone secretion was dependent on the degree of follicular development, as determined by peripheral oestradiol concentrations, on the day of laparoscopy. These results suggest that adrenaline and melatonin may have a physiological role in modulating luteal function and that melatonin may act by a beta-adrenergic-related mechanism.

Effect of an inhibitor of 3 beta-hydroxysteroid dehydrogenase on progesterone concentrations and embryo survival in sheep.

The effect of an inhibitor of 3 beta-hydroxysteroid dehydrogenase on peripheral progesterone concentration during the luteal phase of the oestrous cycle and on embryo survival was determined in sheep. Following administration of 10, 50, 100 or 250 mg epostane (4,5-epoxy-17-hydroxy-4,17,dimethyl-3-oxo-androstane-2-carbonitrile) progesterone concentrations were significantly lower than control levels 4 h after injection, from 2.5 to 22 h, 1.5 to 24 h and 1 to 24 h after injection respectively. There appeared to be no effect on peripheral oestradiol concentrations. Adrenal progesterone production was small and not influenced by epostane treatment. Epostane was administered on day 9 of the oestrous cycle to cause a reduction in progesterone concentrations for approximately 12-18 h on day 9 only (group 1, 250 mg epostane on day 9), or a series of such reductions on 3 consecutive days (group 2, 50 mg epostane on days 9, 10 and 11) or a continuous reduction for 3 days (group 3, 250 mg epostane on days 9, 10 and 11). The proportion of ewes that were pregnant was significantly (P less than 0.05) lower in ewes treated to give a continuously low progesterone concentration for 3 days than in either controls or ewes in which progesterone concentration was reduced for less than 24 h (in controls and groups 1, 2 and 3 the proportion was 85, 92, 54 and 18% of ewes treated respectively). Embryo survival was not affected by administration of 250 mg epostane on days 9, 10 and 11 if luteal phase levels of progesterone were maintained by insertion of a silicone elastomer implant of the steroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperprolactinemia induced by an estrogen-progesterone synergy: quantitative and temporal effects of estrogen priming in monkeys.

We evaluated the quantitative and temporal characteristics of the estrogen component of an estrogen-progesterone synergy, which can induce hyperprolactinemia in macaques. In Exp I, six groups of monkeys were treated for 2 weeks with various doses of estradiol benzoate (EB), which resulted in peripheral estradiol concentrations of 250-1500 pg/ml, followed by 2 weeks of combined estrogen and progesterone treatment. In each of the groups, regardless of the dosages of estradiol benzoate alone, PRL concentrations remained within normal limits (approximately 18 ng/ml). In contrast, during the subsequent period of combined EB and progesterone therapy, hyperprolactinemia developed. The resultant PRL concentrations were not dependent on the dose of EB administered. In Exp II, three groups of monkeys were treated with EB (25 micrograms/kg) alone for various intervals and subsequently with both EB and progesterone for 14 days. When initiation of progesterone therapy was preceded by a 9- or 6-day period of estrogen priming, PRL concentrations were significantly (P less than 0.05) elevated within 3-4 days; in contrast, when the EB and progesterone treatments were initiated simultaneously, 8 days elapsed before the PRL elevations were significant. In a third experiment, to determine whether decidualized endometrium accounted for the increased PRL levels following estrogen and progesterone treatment, a hysterectomized monkey was treated with EB followed by combined EB and progesterone treatment. The PRL response was not different from that of intact monkeys similarly treated. From these findings we conclude 1) that the estrogen-progesterone synergy promoting PRL secretion is not of endometrial origin; 2) that approximately 1 week of estrogen priming is required for progesterone to induce PRL secretion; 3) and that the mode of action of estrogen is not dose dependent, but, rather, is a threshold effect.

Rapid endocrine effects of tamoxifen and testolactone in prostatic carcinoma patients.

The short-term (6-day) endocrine effects of tamoxifen and testolactone were investigated in men with prostatic carcinoma. Tamoxifen treatment (20 mg/day) did not affect the gonadotropin levels, but it temporarily increased prolactin, induced sex hormone-binding globulin production, and suppressed peripheral serum progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and 5 alpha-dihydrotestosterone concentrations. These changes were attributed to the estrogenic properties of tamoxifen, since no changes in peripheral serum estradiol concentrations were observed. Testolactone (1000 mg/day) decreased peripheral estradiol concentrations by 50% and increased the concentrations of the neutral steroids measured. The increases in serum FSH and LH were very small. This study corroborates the early estrogen-like action of tamoxifen, and the experiment with testolactone further suggests that endogenous estradiol has physiological functions in man, regulating gonadotropin and androgen production.

Differential Responsiveness to LRF after Estrogen Therapy in Women with Hypothalamic Amenorrhea

Ten amenorrheic and eight normally cycling women were challenged with a 10-jug doseof synthetic LRF before and after a short 3- to 5-day course of ethinyl estradiol (1.0–1.5 /µg/kg/day). In normally cycling women tested on day 5 of the menstrual cycle, significant augmentation of the LRF-induced LH but not FSH response was observed after estradiol treatment. The amenorrheic patients all had normal or reduced levels of serum gonadotropins, no evidence of galactorrhea, and no other endocrine abnormality. Responses to LRF inthe amenorrheic women were easily segregated into two groups after treatment with estrogen: those with significantly augmented LH response (P < 0.05) and others with markedly diminishedresponses (P < 0.005) when compared with responses to LRF before estrogen treatment. The response patterns for FSH were similar although not so pronounced. That group of amenorrheic women with augmented LRF-induced LH response had peripheral estradiol concentrations of 15 pg/ml or more and responded to clomiphene citrate with a doubling in serum gonadotropin levels. The five women with diminished LRF-induced gonadotropin response had essentially undetectable circulating levels of serum estradiol (<15 pg/ml). The differential LRF-induced responses observed in this study suggest that gonadal steroids may exert a direct effect on gonadotrophs in terms of both the dose and duration of exposure. Moreover, although these data suggest that patients with hypothalamic amenorrhea may be subdivided into two groups, there is some evidence that such patients may represent a continuum from minimal hypothalamic dysfunction to a frankly unresponsive hypothalamic-pituitary axis.