Subcutaneous Oestradiol Implants Research Articles

Androgen receptor is essential for sexual differentiation of responses to olfactory cues in mice

During sexual differentiation males and females are exposed to different levels of testosterone, which promotes sex differences in the adult brain and in behavior. Testosterone can act after aromatization or reduction via a number of steroid hormone receptors. Here we provide new evidence that the androgen receptor (AR) is essential for sexual differentiation in mice. We used mice carrying the testicular feminization (Tfm) mutation of the AR. Adult Tfm males, wild-type male and female littermates were gonadectomized and given subcutaneous estradiol implants. In all sexually dimorphic traits, Tfm males had responses equivalent to females and different from males. In simultaneous choice tests, males spent significantly more time investigating female-soiled bedding, whereas females and Tfm males preferred to investigate male-soiled bedding. Tfm males and females did not have a partner preference in tests with awake stimulus animals, whereas males showed a preference for females over males. Exposure to male-soiled, but not clean, bedding produced a significant increase in c-Fos-immunoreactive cells in the medial preoptic area and bed nucleus of the stria terminalis in Tfm males and females, no increase was noted in males. Masculine sexual behavior (mounting and thrusting) was not sexually dimorphic, and all groups displayed these behaviors. Our results support data collected in humans suggesting a role for the androgen receptor in sexual differentiation of social preferences and neural responses to pheromones.

Effect of estradiol implants on reproductive behavior of female Lapland longspurs ( Calcarius lapponicus)

The role of estrogens in reproductive behavior of free-living birds has been little investigated, despite the importance of estrogens in coordinating reproductive behavior and the need for information on potential effects of estrogenic contaminants on wildlife. We gave subcutaneous implants of estradiol (E 2) to 15 female Lapland longspurs ( Calcarius lapponicus), an arctic bird with a six-week breeding season. Controls were 9 females with empty implants and 14 unimplanted females. After implantation, E 2 females had greater E 2 levels and greater body mass than controls. We did not detect any increases in, or prolongation of, sexual or nest-building behavior. The incubation period was longer for E 2 nests than for control nests. Nest videotapes showed that E 2 females and their mates exhibited normal nestling care, and nestling growth, fledging success, and overwinter survival were also unaffected. However, whenever the males arrived at the nests, E 2 females showed a significantly greater likelihood of begging from the male rather than leaving the nest. Courtship or incubation feeding have been considered atypical for this species, and it is not clear what role E 2 normally plays in promoting begging behavior. Overall, elevated E 2 levels did not result in any obvious costs for the female, save perhaps for slightly reduced incubation efficiency. The weak response to hormonal implants is similar to patterns seen in male Lapland longspurs, and may be related to the short breeding season. However, since little is presently known about the role of estrogens in behavior of wild female birds, it remains to be seen whether these patterns are typical of female passerines in general, or of short-season breeders. Further research on effects of estrogens (both exogenous and endogenous) on free-living female birds is needed.

The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women

Objective To evaluate the anabolic effect of oestrogen on bone by comparing the response of markers of bone formation (and resorption) and bone mineral density (BMD) to subcutaneous oestradiol implants. Design One year double-blind placebo controlled randomised study. Setting Clinical research unit within a teaching hospital. Population Twenty-one hysterectomised postmenopausal women were randomised to 25 mg oestradiol implants at baseline and at six months or to have a sham procedure at baseline and six months. Methods BMD and quantitative ultrasound (QUS) were assessed at baseline and one year. Bone alkaline phosphatase (bone ALP), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), free deoxypyridinoline (iFDPD), N-telopeptide of type I collagen (NTX), serum oestradiol and intact parathyroid hormone (PTH) were measured at baseline, 4, 8, 12 and 24 weeks. Main outcome measures Percentage change markers of bone turnover and PTH and change in oestradiol levels over first six months and percentage of changes in DXA and QUS over one year. Results PINP, bone ALP and OC increased by 28%, 7% and 9%, respectively ( P < 0.01) during the first four weeks of treatment and then decreased significantly. Lumbar spine (LS) and total hip (TH) BMD increased by 5.4% and 6.0% ( P < 0.001), respectively, and femoral neck (FN) BMD by 3.7% ( P < 0.05) during the first year of treatment compared with control subjects. The peak serum oestradiol level was achieved four weeks after implant insertion. Mean PTH levels increased significantly in subjects receiving subcutaneous oestradiol. Conclusion Subcutaneous oestrogen exerted an apparent anabolic effect on bone, which was initially reflected by an increase in bone formation markers and later by a large increase in BMD.

Steroid-dependent up-regulation of adipose leptin secretion in vitro during pregnancy in mice.

Circulating leptin levels are elevated during the later stages of pregnancy in mammals, suggesting that maternal leptin may play a role in maintenance of pregnancy and/or preparation for parturition and lactation. The regulation and source of circulating leptin during pregnancy remains undetermined, but leptin mRNA levels increase in adipose tissue during this time in some species. Considerable controversy exists whether placenta is also a leptin-secreting tissue during pregnancy. Here, we directly demonstrate that leptin secretion rates from mouse adipose tissue in vitro are decreased during early pregnancy and up-regulated during late pregnancy and lactation. Changes in leptin secretion rates in vitro paralleled those of circulating leptin in vivo during gestation. Subcutaneous implants of estradiol or corticosterone into lactating mice for 48 h stimulated adipose leptin secretion rates in vitro to the level of that in pregnant mice. However, corticosterone, but not estradiol, increased leptin secretion when added to isolated adipose tissue in vitro. Placentae obtained at two stages of pregnancy did not secrete leptin in vitro, either when acutely isolated or when dissociated into cells for long-term cultures. Placental tissue (or cells) secreted progesterone, however, demonstrating placental viability. We conclude that hyperleptinemia during late pregnancy in mice primarily results from corticosterone-dependent up-regulation of leptin secretion from adipose tissue, and that the placenta does not contribute to leptin secretion. The initial decrease in leptin secretory rates from adipose tissue during early pregnancy may facilitate energy storage for the subsequent, increased metabolic demands of later pregnancy and lactation.

Inhibition of luteinizing hormone secretion and expression of c-fos and corticotrophin-releasing factor genes in the paraventricular nucleus during insulin-induced hypoglycaemia in sheep.

Insulin can act within the brain to stimulate ovine luteinizing hormone (LH) secretion, but insulin-induced hypoglycaemia inhibits LH via unknown brain sites, possibly involving corticotrophin-releasing factor (CRF). Castrate male sheep, with (E+) or without (E-) subcutaneous oestradiol implants, were blood sampled every 12 min for 8 h. Insulin (0.25 or 0.5 IU/kg) was injected at 4 h via the carotid artery or jugular vein. All treatments reduced LH output with no differences between dose rate nor route of administration, but sensitivity was greater in E+ than E-sheep. There was no evidence for an effect of insulin on LH 0-1 h postinjection; however, 1-3 h after insulin, when hypoglycaemia was established, LH pulses were inhibited in both E+ and E- sheep (P<0.001). Additional intravenous (i.v.) glucose injections given 1 h (20 mmol) and 2 h (10 mmol) after insulin (0.5 IU/kg) were each followed by an LH pulse within 30 min (75% response in both E+ and E-sheep). In a separate experiment, sheep were killed 2 h after i.v. insulin (0.5 IU/kg) or saline. In-situ hybridization revealed c-fos mRNA in the paraventricular nucleus (PVN), but not in any other hypothalamic nuclei nor in the hindbrain; and this was linked with increased CRF gene expression in the PVN. Similar c-fos and CRF gene expression was seen in insulin-treated sheep given additional i.v. glucose (20 and 10 mmol, respectively, 40 and 20 min ante mortem), but not in saline-treated controls. Therefore, insulin-induced hypoglycaemia inhibited LH secretion, with oestradiol potentiating the effect, and was associated with gonadal steroid-independent c-fos gene expression and increased CRF gene expression in the PVN. The ovine PVN may be involved in mediating insulin-induced hypoglycaemic inhibition of LH by a mechanism which might involve CRF.

Effects of insulin-like growth factor-1 on luteinizing hormone secretion in sheep.

Circulating insulin-like growth factor-1 (IGF-1) may be involved in nutritional modulation of reproductive status. Acute effects of IGF-1 on luteinizing hormone (LH) secretion were studied in two experiments, each using eight castrate male sheep surgically prepared with an elevated carotid artery, four with (E+) and four without (E-) subcutaneous oestradiol implants. Blood samples were taken every 12 min for 8 h at weekly intervals, with IGF-1 given at 4 h. In Experiment 1, sheep were fed to maintain live weight (maintenance) and IGF-1 doses tested were 25, 50, 100 and 150 micrograms kg-1 given via the carotid (i.c.). Plasma LH concentrations were 6.2 +/- 0.35 (E-) and 4.2 +/- 0.49 (E+) ng ml-1 pre-IGF-1, were increased after 25 micrograms kg-1 IGF-1 (E-, 15%; E+, 11%) but were either unaltered (E-) or decreased (E+, -16%) after 150 micrograms kg-1; thus, mean LH response was negatively related to IGF-1 dose (E-, b = -0.007, P < 0.01; E+, b = -0.011, P < 0.05). LH pulse frequencies (p.f.) were 4.6 +/- 0.42 (E-) and 3.9 +/- 0.35 (E+) pulses per 4 h pre-IGF-1, were unaltered after 25 micrograms kg-1 IGF-1, but were decreased after 150 micrograms kg-1 (E-, -33%; E+, -51%); thus, p.f. was also negatively related to IGF-1 dose (E-, b = -0.016, P < 0.01; E+, b = -0.019, P > 0.05). LH pulse amplitude and baseline were not significantly altered by IGF-1. Plasma glucose concentrations decreased after 100 and 150 micrograms kg-1 IGF-1 from 3.40 to 2.50 and 2.34 mmol l-1, respectively (SED 0.314, P < 0.001), but were not significantly altered after lower doses. Thus, hypoglycaemia caused LH inhibition after higher doses of IGF-1, which counteracted (E-) or overcame (E+) the stimulatory effects on LH seen after lower doses. In Experiment 2, sheep were fed 50% maintenance; saline vehicle i.c., then IGF-1 doses 25 and 50 micrograms kg-1 given i.c. or i.v. were tested. In E- and E+ sheep, respectively, mean LH pre-IGF-1 was 8.7 +/- 0.97 and 1.9 +/- 0.16 ng ml-1, p.f. was 3.8 +/- 0.44 and 0.8 +/- 0.44 pulses per 4 h, and amplitude was 3.6 +/- 0.49 and 0.4 +/- 0.08 ng ml-1. Saline vehicle had no effect on LH. IGF-1 at both doses and by both administration routes in E- sheep increased mean LH (22-29%, P < 0.001), and in E+ sheep increased mean LH (12-36%, P < 0.001), p.f. (94-219%, P < 0.001) and amplitude (125-803%, P < 0.01). Thus, low doses of peripherally-administered IGF-1 stimulated LH output in sheep, consistent with its putative physiological role as a nutritional modulator of reproduction.

Effect of oestradiol and photoperiod on TH mRNA concentrations in A15 and A12 dopamine cell groups in the ewe.

In the sheep, photoperiod, through melatonin, and oestradiol negative-feedback are two major regulators of seasonal changes in luteinizing hormone (LH) and prolactin secretion. Melatonin and oestradiol act on dopamine neurons of the hypothalamus to modify the enzymatic activity of tyrosine hydroxylase (TH). To further understand how melatonin and oestradiol regulate TH activity, we have studied the level of TH mRNA by in situ hybridization with an homologous cDNA probe, in A12 and A15 dopamine neurons of four groups of ovariectomized ewes: long-day exposed ewes with or without subcutaneous oestradiol implants and short-day exposed ewes with or without oestradiol. Results were analysed in relation to the concentration of LH and prolactin in the peripheral circulation. In the A15 cell group, TH mRNA levels were elevated in the short-day, oestradiol-treated ewes compared to all other groups. In this group, the level of TH mRNA was elevated simultaneously with LH concentration. The low level of TH mRNA found in the long-day, oestradiol-treated ewes may indicate that the increase of TH enzymatic activity previously reported by this treatment is not caused by an increase of the level of enzyme. In the A12 cell group, the level of TH mRNA in both long-day and short-day oestradiol-treated ewes was significantly higher than in ewes without oestradiol replacement. Prolactin concentrations were not correlated with TH mRNA variations in the A12 cell group.

Characteristics of the plasma melatonin rhythm are not modified by steroids during the estrous cycle in IIe-de-France ewes.

Two experiments were designed to determine whether gonadal steroids during the estrous cycle may modify the characteristics of the plasma melatonin rhythm. In the first experiment, 12 ovariectomized estradiol-treated ewes were used and exposed to constant short days. The experimental design was a latin square to distinguish between steroid treatments and individual effects on melatonin secretion. Twenty four hours before the bleeding period (hourly during 20 hr) and with a 1 week interval, animals were treated with a) additional subcutaneous estradiol implants, b) progesterone devices, or c) control. In the second experiment, nine ewes received a treatment combining fluorogestone acetate devices and pregnant mare serum gonadotrophin to induce synchronous ovulations. Samples for melatonin determination were obtained hourly for 13 hr at three stages of estrous cycle: follicular phase, early luteal phase, and late luteal phase. Ovarian activity was monitored by taking daily samples for progesterone analysis and ovulation rate was determined by laparoscopy. Duration and mean melatonin plasma concentrations of the elevation were calculated for each ewe and each night and analysed by latin square test (experiment 1) or ANOVA (experiment 2). Melatonin concentrations of elevation and duration of elevation were not significantly affected by hormonal treatments or by phase of estrous cycle. A strong individual effect was detected (P < 0.01) for both parameters in both experiments. It was concluded that melatonin secretion is unaffected by steroid administration or by phase of estrous cycle. The existence of very high inter-individual variation suggest that both parameters are individual characteristics of each animal which may have a strong genetic basis.

Messenger ribonucleic acid for gonadotropin-releasing hormone receptor and numbers of gonadotropin-releasing hormone receptors in ovariectomized ewes after hypothalamic-pituitary disconnection and treatment with estradiol.

To study the regulation of ovine GnRH receptors in the absence of GnRH, hypothalamic input was removed by hypothalamic-pituitary disconnection (HPD). Steady-state concentrations of GnRH receptor mRNA and numbers of GnRH receptors were measured after HPD and subsequent treatment with estradiol. Anterior pituitary glands were collected 24 (n = four), 36 (n = two), 48 (n = four), and 72 h (n = four) after HPD. An additional group of ewes received subcutaneous implants of estradiol 24 h after HPD, and pituitary glands were collected 0 (n = four), 12 (n = four), 24 (n = three), and 48 h (n = four) after exposure to estradiol. Pituitary glands were also obtained from four ovariectomized ewes that did not undergo HPD (OVX controls). At 24 h after HPD, mean number of GnRH receptors had decreased (P < .05) by 73%; however, mean concentration of GnRH receptor mRNA was not different from OVX controls. Relative to HPD ewes, treatment with estradiol increased mean concentrations of GnRH receptor mRNA and mean numbers of GnRH receptors (P < .01 and P < .001, respectively). From these data we conclude that 1) acute removal of GnRH decreases the numbers of GnRH receptors but does not affect steady-state concentrations of GnRH receptor mRNA and 2) estradiol increases the numbers of GnRH receptors and steady-state concentrations of GnRH receptor mRNA via direct effects at the level of the pituitary gland.

Estradiol implants, hormone levels and reported symptoms

Subcutaneous estradiol implants are used to give hormone replacement therapy following hysterectomy and oophorectomy. They may be renewed when symptoms return or when estradiol levels fall. Eighteen women who had requested renewal of implants were assessed on a number of endocrine and psychological measures. All except one reported psychological or vasomotor symptoms but only two had estradiol levels below the normal menstrual range of 200-800 pmol/1. Twelve reported vasomotor symptoms and had lower levels of estradiol but were no different on psychological measures. Symptom rating scores, personality scores and anxiety scores were not related to estradiol levels. Two case histories describe symptoms in women with supraphysiological levels of estradiol. Women who had levels of estradiol within normal range yet reported hot flushes were no more 'anxious' or 'neurotic' than those not reporting hot flushes. Six women requested renewal of the estradiol implant who did not have vasomotor symptoms or vaginal dr...

Thecal and interstitial cells in polycystic ovaries (PCO) in the rat

Two different types of experimentally-induced polycystic ovaries (PCO) have been examined. A macrocystic ovarian condition is induced by estradiol valerate (EV) injection, whereas a microcystic ovarian condition is engendered with subcutaneous estradiol implants. In both of these models thecal and secondary interstitial cells were characterized using three functionally significant indices. Expression of alkaline phosphatase was evaluated immunohistochemically, hCG/LH-binding capacity was assessed by means of EM radioautography, and the size and percent cytoplasmic area of intracytoplasmic lipid were determined, in the same cells, by morphometry. In both types of ovary, thecal cells of healthy and atretic follicles stained heavily for alkaline phosphatase whereas cystic theca exhibited little or no staining. Intermittent faintly stained patches of secondary interstitial cells, as well as intensely stained spheroidal cell clusters, were most numerous in the microcystic ovary and occurred less frequently in the macrocystic ovary. Cystic thecal cells in both conditions exhibited large lipid droplets and minimal hCG binding. Lipid droplet area was minimal and hCG binding maximal in secondary interstitial cells of both types of ovary. It is concluded that specific clusters of secondary interstitial cells are important steroidogenic elements in PCO, whereas cystic theca is relatively inert.

Effects of levels of food intake and body condition on the sensitivity of the hypothalamus and pituitary to ovarian steroid feedback in ovariectomized ewes

ABSTRACTIn two experiments involving ovariectomized Scottish Blackface ewes and steroid replacement therapy, the effects of level of food intake and of body condition on hypothalamic and pituitary sensitivity to progesterone and oestradiol feedback were investigated. In experiment 1, groups of 16 ewes in similar levels of body condition were given dried grass pellets ad libitum (mean dry-matter (DM) intake of 2481 (s.e. 71) g per head per day; group H) or 1105 g DM per head per day (group M). In experiment 2, groups of 16 ewes were fed so that they achieved body condition scores of 2·70 (s.e. 0040; group HBC) or 1·67 (s.e. 0·036; group LBC) prior to the start of the experiment. All ewes were then fed to maintain their respective levels of body condition. In both experiments, all ewes were ovariectomized and intravaginal progesterone pessaries and subcutaneous oestradiol implants were inserted; these were designed to induce circulating concentrations of these steroids within the normal range for intact ewes. Approximately 1 week later, blood samples were collected at 15-min intervals for 10 h, and at 10-min intervals for 8 h before and after pessary withdrawal respectively. All samples were assayed for LH and selected samples were assayed for FSH and progesterone. Gonadotropin profiles were also recorded during 2-h periods following injection (i.v.) of 0·25 μg and 5 μg GnRH. When circulating progesterone concentrations were elevated, due to the presence of a progesterone pessary, there was no effect of level of food intake on mean LH or FSH concentrations or mean LH pulse frequency but H ewes had a higher mean LH pulse amplitude than M ewes (P &lt; 005). When the progesterone pessaries were absent, H ewes had a higher mean LH concentration (P &lt; 001), mean LH pulse frequency (P &lt; 001) and LH pulse amplitude (P &lt; 0·01) than M ewes but mean FSH concentrations were similar in the two groups. Irrespective of the presence or absence of elevated progesterone concentrations, the pituitary responses to GnRH injection were either not significantly different or were lower in H compared with M ewes. In experiment 2, HBC ewes had a higher mean LH concentration (P &lt; 001), LH pulse frequency (P &lt; 0·001), pulse amplitude (P &lt; 0·001) and FSH concentration (P &lt; 001) than LBC ewes, irrespective of circulating progesterone concentrations. The mean heights and ‘areas’ of the LH peak induced by injection of 0·25 μg GnRH were larger in HBC than LBC ewes (P &lt; 005) irrespective of circulating progesterone concentrations. When mean concentrations before injection were taken into account, the corresponding increases in FSH concentration were similar for the two groups. Following injection of 5 u.g GnRH, the differences in peak size were generally not significant. It is concluded that during the follicular phase of the cycle, a low level of intake is associated with increased hypothalamic sensitivity, but not pituitary sensitivity to oestradiol feedback. Body condition affects both hypothalamic and pituitary activity but the relative importance of direct and indirect effects of body condition on the sensitivity of these organs to steroid feedback, remains to be elucidated.

Interactions of Sex Steroid Hormones and Prolactin in Male and Female Song Sparrows, Melospiza melodia

Subcutaneous implants of estradiol in female song sparrows, Melospiza melodia, maintained sexual receptivity throughout the breeding season. Parental behavior apparently was not affected. Estrogenized females continued to incubate and feed young Plasma levels of prolactin were also unaffected by estrogen treatment. Male song sparrows mated to estrogenized females maintained high levels of testosterone throughout much of the breeding season. Only in late June and early July were testosterone levels in experimental males similar to those of controls. By July, however, levels of testosterone were again elevated significantly over those of controls. These data agree with other investigations showing that continual exposure of males to sexually receptive females maintains high levels of testosterone. The rise in prolactin in males was not affected by high circulating concentrations of testosterone, and changes in prolactin levels throughout the breeding season in experimental males were similar to the control cycle. It is concluded that in the song sparrow, elevated levels of prolactin during breeding do not inhibit secretion of sex steroids, nor do experimentally induced high circulating titers of sex steroid hormones alter seasonal changes in prolactin secretion.

Seasonal and hormonal control of pulsatile LH secretion in the dairy goat (Capra hircus)

In Exp. 1, the changes in pulsatile LH secretion at the onset of the breeding season were observed in 20 intact, mature Saanen does. Blood was sampled every 20 min for 6 h each week from the beginning of August until the onset of ovulatory activity, as evidenced by cycles in plasma progesterone. The first doe ovulated at the end of August and all were cycling by the end of September. As the first ovulation approached, LH pulse frequency increased by 67% and mean levels of LH increased by 47%. These changes were progressive rather than abrupt. In Exp. 2, seasonal changes in the inhibition of pulsatile LH secretion by ovarian steroids were studied in ovariectomized Saanen does. The animals were untreated (N = 4) or given subcutaneous oestradiol implants (N = 4) and blood was sampled every 10 min for 6 h, twice during the breeding season and twice during the anoestrous season. In each season, the second series of samples was taken after the animals had been treated with progesterone, administered by intravaginal implants. Season did not significantly affect LH secretion in goats not treated with oestradiol, but LH pulse frequency was 54% lower during the anoestrous season than during the breeding season in oestradiol-treated goats. Mean LH concentrations were affected in the same manner as pulse frequency, but pulse amplitude was increased by oestradiol treatment in both seasons. Progesterone had no detectable effect on LH secretion in either season. In Exp. 3, the response to repeated melatonin injections at a set time after dawn was investigated in 11 oestradiol-treated, ovariectomized goats.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrous cycle variations in levels of cholecystokinin immunoreactivity within cells of three interconnected sexually dimorphic forebrain nuclei. Evidence for a regulatory role for estrogen.

The central part of the medial preoptic nucleus (MPNc), the encapsulated part of the bed nucleus of the stria terminalis (BSTe), and the posterodorsal part of the medial nucleus of the amygdala (MeAp) are all though to be involved in the neural control of female reproductive behavior, as well as other neuroendocrine mechanisms. Although the developmental importance of gonadal steroids during the perinatal period on these sexual dimorphisms is well known, an understanding of possible activational effects on these cell groups of circulating gonadal steroids in the adult is less clear. In the present study we evaluated the number of cholecystokinin (CCK)-immunoreactive cells present within MPNc, BSTe, and MeAp of regularly cycling female rats over the estrous cycle. In addition, the effects of ovariectomy and estrogen replacement on CCK staining were also examined. The number of CCK-immunoreactive cells within each cell group varied over the estrous cycle with the fewest cells present in animals sacrificed while in diestrus. Proestrous female rats showed a greater number of cells within each nucleus, while intermediate numbers were found for animals in estrus. These changes appear to be due, at least in part, to changes in levels of circulating estrogen, since subcutaneous implants of estradiol prevented the decline in the number of CCK-stained cells within MPNC, BSTe, and MeAp that was seen in untreated, ovariectomized female rats. Thus, the present findings support the hypothesis that levels of CCK within cells of these three sexually dimorphic cell groups are regulated by circulating gonadal steroids within a physiologically relevant time frame and may possibly contribute to the activation of female reproductive behavior as well as other neuroendocrine functions.

Effects of subcutaneous oestradiol implants on ovarian activity.

The effects of subcutaneous oestradiol implants on ovarian activity were investigated in 14 ovulating premenopausal women. Treatment with either 100 mg or 150 mg oestradiol was combined with cyclical oral norethisterone from days 20 to 26 of the cycle to ensure regular withdrawal periods and prevent endometrial hyperplasia. Ovarian function was monitored by regular pelvic ultrasonography and urinalysis over a period of nine cycles. During the first three cycles after hormone implantation, follicular development continued in almost half the study group, but only one of the women in each treatment group showed signs of follicular rupture and luteinization. By the sixth cycle, over half the women given the lower dose of oestradiol were developing follicles, including a large functional cyst in one, but none of them ovulated. A further implant given early in the seventh cycle was associated with ovarian suppression in all cases. Both doses of implant elevated the excretion of oestrone-3-glucuronide compared to pretreatment. The contraceptive and therapeutic implications of these results are discussed.

Cellular and tissue mechanisms of primate uterine endometrial renewal: an hypothesis.

Recent advances in hormonal regulation of cyclic uterine differentiation and preimplantation biology are evident in the remarkable announcements that normal live primate newborns can be produced through artificial menstrual cycles in ovariectomized rhesus monkeys and women (1–3). Such fertile menstrual cycles are produced in rhesus monkeys by a program of insertion and removal of subcutaneous silastic implants of estradiol and progesterone that serve as effective “artificial ovaries” until the placenta takes over the maintenance of pregnancy. These tangible demonstrations provide new stimulus for experimental analysis of endometrial cell and tissue compartments in the primate (rhesus) uterus with regard to the hormonal mechanisms that control cyclic renewal.

Effects of implants of oestradiol plus progesterone on the growth rate and intramuscular fat composition of steers raised in southern Australia

At 3 experimental sites in South Australia and Victoria beef steers at pasture received subcutaneous implants of oestradiol (20 mg) plus progesterone (200 mg) in the ear and were raised with untreated animals for about 100 days. Implanted animals showed responses in liveweight gain 10-23% greater than untreated animals. The least response (0.10 kg/ steer.day) was recorded at Roseworthy Agricultural College in South Australia, which has the shortest growing season (7 months). The maximum response (0.19 kg/steer.day) was recorded near Mt Pleasant in South Australia which has a more temperate climate than Roseworthy, but a shorter growing season than a site in Victoria (near Molesworth) where untreated animals had the highest growth rates (1.07 kg/ steer.day). Analysis of intramuscular lipid showed that the ratio of saturated to polyunsaturated fatty acids was significantly correlated (P&lt; 0.01) with the final liveweight of both the treated and untreated steers (r = 0.82). Our results demonstrated that oestrogenic implants were effective in steers in southern Australia. They were most effective in older animals that weighed more than 180 kg at implantation and were entering the fattening phase of their development. Oestrogenic hormone treatment increased growth rate but did not increase (nor decrease) fat deposition in animals of the same weight (P&gt; 0.01).

Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical norethisterone

Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical norethisterone

Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical oral norethisterone.

Treatment of the premenstrual syndrome by subcutaneous oestradiol implants and cyclical oral norethisterone.