Influence Of Sex Steroids Research Articles

Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism by neonatal testosterone.

The influence of endogenous sex steroids and exogenous testosterone treatment on pulsatile GH secretion, body weight, longitudinal bone growth, and hepatic steroid metabolism was studied in male and female adult rats. Blood samples were obtained from the tip of the tail, and maximum and minimum GH levels were determined in individual rats to evaluate pulse heights and baseline levels. Longitudinal bone growth was measured using the intravital marker tetracycline, and hepatic steroid metabolism was evaluated by determining the enzyme activities of 16 alpha-hydroxylase and 5 alpha-reductase. Neonatal, but not prepubertal, gonadectomy of male rats suppressed maximum and mean plasma GH levels during adult life. The body weight and the rate of longitudinal bone growth were also decreased. Testosterone treatment neonatally reversed all of these effects. Neonatal gonadectomy of male rats also caused an elevation of minimum plasma GH levels, an effect, however, which was not reversed by testosterone replacement during neonatal life. Neonatally gonadectomized females treated with testosterone neonatally or during adult life increased their maximum and decreased their minimum GH levels. Their longitudinal bone growth was increased. The body weight of these rats was increased by neonatal, but not adult, testosterone treatment. There was no effect of neonatal ovariectomy on plasma GH levels in 3- to 4-month-old female rats. However, neonatal ovariectomy did increase the maximum and mean plasma GH levels immediately postpubertally, suggesting that the effect of the ovaries on GH secretion differs among mature female rats of different ages. Prepubertal gonadectomy of male rats feminized their hepatic steroid metabolism by decreasing 16 alpha-hydroxylase and increasing 5 alpha-reductase activities. Neonatal gonadectomy caused an even more pronounced feminization, which was partly reversed in rats given testosterone replacement therapy neonatally. In neonatally gonadectomized female rats, treatment with testosterone during adult life increased 16 alpha-hydroxylase and decreased 5 alpha-reductase to levels seen in intact male rats. The present results indicate that neonatally secreted testicular androgens imprint the high amplitude pulses characteristic of GH secretion in adult male rats. Neonatal androgens also stimulate somatic growth and partially account for the masculinized hepatic steroid metabolism in the adult animal. It is proposed that imprinting of the GH secretory pattern contributes to the influence of neonatal testicular androgens on body growth and hepatic steroid-metabolizing enzymes.

Estradiol increases growth hormone secretion in rats exposed to swimming stress or reserpine treatment

The secretory pattern of growth hormone (GH) in female rats differs from that in males with respect to e.g. the inter-peak baseline levels being higher in females. In the present study the influence of sex steroids on plasma GH levels was investigated in male rats under various conditions. Administration of estradiol, but not testosterone, was found to increase GH release in rats with suppressed levels induced by exposure to swimming stress or by treatment with the monoamine depleting agent reserpine. In line with previous studies, administration of estradiol was found to increase also inter-peak GH levels in adult male rats; i.e. to cause a feminization of the secretory pattern. In stressed and in reserpinized animals as well as in normal male rats, the effect of estradiol is similar to that earlier demonstrated for somatostatin antiserum, and hence it is suggested that estradiol may act antagonistic to the GH inhibiting factor.

Ultrastructural study of cultured smooth muscle cells from uterine leiomyoma and myometrium under the influence of sex steroids

Upon the hypothesis that the differentiation or development of smooth muscle cells in both myometrium and leiomyomas may be under the regulation of sex steroids, myometrial and myoma cells were cultured in the presence of sex steroids and their morphological changes were studied ultrastructurally. The cells from the explants of both leiomyoma and myometrium at the 14th day in either control or E (10 −8 M 17-β-estradiol)-added medium showed extremely well-developed cytoplasmic organelles with few filaments located at the marginal portion of the cytoplasm. These ultrastructural features resembled those of a dedifferentiated stage of smooth muscle cells in vitro. At the 21st day, these cells showed a moderate number of cytoplasmic filaments with dense bodies. These ultrastructural features resembled those of a redifferentiated stage of smooth muscle cells in vitro. In both E- and P (10 −7 M progesterone)-added medium, the cultured smooth muscle cells from both leiomyoma and myometrium showed an increased number of myofilaments with dense bodies even at the 14th day to the 21st day of culture in comparison to the cells either in control or estrogen-added medium. Therefore, the cultured smooth muscle cells in the medium with E and P lacked their dedifferentiated phase in vitro and/or the differentiation or maintenance of their filaments might be under the influence of both estrogen and progesterone. On the observation that the cultured smooth muscle cells from both leiomyoma and myometrium showed very similar ultrastructural changes under the influence of sex steroids, it was suggested that leiomyoma may have the same progenitor cells as myometrium.

Influence of pregnancy and sex steroids on concentration, motor effect and receptor binding of VIP in the rabbit female genital tract.

The influence of sex steroid and pregnancy on the tissue concentration, uterine motor effect and receptor binding of VIP has been studied in the female genital tract of pregnant rabbits and oophorectomized rabbits during progesterone and/or oestrogen substitution. The concentration of immunoreactive VIP was high in the vagina and cervix, and lower in the uterine body of both pregnant and non-pregnant rabbits. A significant decrease in the VIP concentration (pmol/g wet weight) of the uterine body was observed toward term of pregnancy. The total uterine content of VIP, however, seems unchanged. Treatment of oophorectomized rabbits with ovarian steroids had no effect on the VIP concentration. The sensitivity for and potency of VIP on the relaxation of uterine muscle was significantly higher in oophorectomized rabbits treated with a combination of progesterone and oestrogen than in control rabbits. No difference was observed between non-pregnant and pregnant rabbits. The degradation and binding affinity for 125I-labelled VIP was highest in oophorectomized rabbits substituted with both oestrogen and progesterone. In the pregnant rabbits, the amount of receptors was decreased near term. In conclusion, sex steroids are able to influence the motor effect of VIP at the receptor level, but have no effect on the VIP concentration in the female genital tract.

Calmodulin concentration in the uterus during pregnancy and influence of sex steroids.

Calmodulin concentration in pregnant rat uteri increased gradually and reached a level about three times that in non-pregnant rat at term. In human beings, uterine calmodulin content at term was about three times that in non-pregnant uteri, but there was no significant difference between the levels in uteri at term with and without labor pain. Estrogen increased the rat uterine calmodulin concentration, but progesterone did not change it.

Influence of pregnancy and sex steroids on concentration, motor effect and receptor binding of VIP in the rabbit female genital tract

Influence of pregnancy and sex steroids on concentration, motor effect and receptor binding of VIP in the rabbit female genital tract

Influence of sex and sex steroids on bilirubin uridine diphosphate-glucuronosyltransferase activity of rat liver

Bilirubin uridine diphosphate-glucuronosyltransferase activity was markedly higher in liver preparations of adult female rats when compared with adult male rats. Ovariectomy decreased the levels in females whereas orchiectomy produced an increase in males. Totally opposite results were obtained when assaying p-nitrophenol uridine diphosphate-glucuronosyl-transferase; this suggests the existence of different enzymes. Administration of physiologic amounts of testosterone decreased enzyme activities in orchiectomized males to normal levels. Estradiol had no effect but progesterone significantly enhanced the transferase activity of gonadectomized females. The effect was more pronounced when progesterone was associated with estradiol. The combined treatment of ovariectomized rats resulted in physiologic plasma levels of sex steroids and could increase the levels of glucuronosyl-transferase to values of normal females. Male and female sex hormones thus exert opposite effects on bilirubin uridine diphosphate-glucuronosyltransferase. If applicable to humans, this might explain the differences in serum bilirubin levels in adult men and women, and in the prevalence of Gilbert's syndrome.

Influence of sex steroids on the catecholamine biosynthesis in chromaffin tissue from rainbow trout, Salmo gairdneri

The in vitro activities of dopamine-β-hydroxylase (DBH) and phenylethanolamine- N-methyl transferase (PNMT) were determined in the chromaffin tissue (head kidney) of sex steroid-treated rainbow trout, Salmo gairdneri. In addition, the DBH and PNMT activities were measured in fish at different sexual states. Steroid treatment increased the wet weight of the head kidney, while both DBH and PNMT activities decreased. Although no sex difference in the enzyme activities was detected, a possible correlation between DBH and PNMT activities and increased GSI values was indicated. The presented data suggest that changes in sex steroids during development may affect the catecholamine synthesis in the chromaffin tissue in S. gairdneri.

Influence of gonadal steroids on age- and sex-related secretory patterns of growth hormone in the rat.

The influence of sex steroids on the pulsatile GH-secretory pattern was investigated in male and female rats of different ages. Neonatal and prepubertal gonadectomy was performed when the rats were 0-1 and 25 days old, respectively. Determinations of plasma GH levels were made in blood samples obtained from the tip of the tail or from a chronic intracardiac venous cannula. After blood sampling from the tip of the tail, maximum and minimum plasma GH levels were determined in individual rats in order to evaluate pulse height and baseline plasma GH levels. In the chronically cannulated rats the GH pulse height and plasma GH baseline levels in individual rats were determined by means of a pulse analysis computer program. Neonatal gonadectomy of male and female rats did not affect the increase in plasma GH that is observed during late prepubertal life in both sexes. However, the pulsatile, sexually differentiated, secretory pattern of GH seen in sexually mature male and female rats was modulated by gonadectomy. In adult male rats, GH was secreted in regular episodes at 3- to 4-h intervals, baseline levels being low or undetectable. After neonatal or prepubertal gonadectomy, GH baseline levels increased in comparison to the sham-operated controls. Replacement therapy with testosterone completely reversed this effect, indicating that a continuous presence of testosterone is necessary for maintaining the low baseline GH levels in adult male rats. Neonatal, but not prepubertal, gonadectomy decreased GH pulse height in male rats during adult life, suggesting that neonatal androgen secretion is a determinant for the pulse height in adult male rats. In female rats, GH pulse height was lower and baseline levels were higher than in male rats. Neonatal gonadectomy resulted in higher plasma GH pulses during puberty and decreased GH baseline levels postpubertally. There were no apparent differences in the GH-secretory patterns between male and female rats after neonatal gonadectomy. Neonatal gonadectomy of male rats decreased body weight gain as well as longitudinal bone growth, as measured in the proximal tibia by the tetracycline method. In contrast, neonatal gonadectomy of female rats resulted in a stimulation of body weight gain and longitudinal bone growth. The present results demonstrate that gonadal steroids influence GH secretion in the rat. We suggest that the sexual differentiation of the GH secretory pattern may be important for the difference in body growth between male and female rats.

Influence of progesterone, androstenedione and oestradiol-17 beta on the incorporation of [3H]proline in the human follicular wall.

The incorporation of proline, a precursor for collagen specific hydroxyproline, is regarded to reflect the metabolism of collagen. In vitro experiments were carried out to investigate the influence of sex steroids on the incorporation of [3H]proline into the human follicular wall. Tissue pieces from the apical wall of follicles at different stages of development were incubated in the presence of the steroids and [3H]proline, and the tissue bound radioactivity was determined. Progesterone induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles. Androstenedione caused a similar effect but only in pre-ovulatory follicles. The influence of oestradiol-17 beta on the incorporation of [3H]proline was less pronounced with a tendency towards a decrease of radiolabelling in both types of follicles. It is suggested that the observed biochemical changes induced by sex steroids are of importance for connective tissue remodelling preceding human follicular rupture.

Influence of sex steroids and prolactin on haloperidol-induced catalepsy

The effects of sex steroids and prolactin on haloperidol-induced catalepsy were investigated in male rats. Repeated administration with estradiol benzoate (5 μg/rat, twice daily for 10 days) significantly potentiated catalepsy induced by 0.25 or 0.5 mg/kg haloperidol, but no effect was observed 10 min or 1 h after a single injection of estradiol benzoate (5 or 50 μg/rat). Conversely, a single administration with the catecholestrogen 2-hydroxyestradiol (50 μg/rat) significantly increased haloperidol-induced catalepsy, suggesting that catecholestrogens may directly interfere with nigrostriatal dopaminergic transmission. Haloperidol-induced catalepsy has been found to be attenuated in conditions of hyperprolactinaemia resulting from anterior pituitary isograft underneath the kidney capsule. This is consistent with the hypothesis that prolactin may stimulate nigro-striatal dopaminergic function. Results obtained also indicate that medroxy-acetate progesterone, a progesterone derivative, may influence haloperidol-induced catalepsy. Specifically, a single administration with medroxy-acetate progesterone (5 mg/kg, i.p.) enhanced catalepsy but opposite effects were observed after repeated administration of medroxy-acetate progesterone (5 mg/kg, i.p., once a day for 7 days).

Influence of sex and oral contraceptive steroids on paracetamol metabolism.

Paracetamol metabolism was investigated in eight healthy males, eight healthy females and eight healthy females receiving oral contraceptive steroids (OCS). Paracetamol clearance was 22% greater in males compared to the control female group. This difference was entirely due to increased activity of the glucuronidation pathway in males, there being no sex-related differences in the sulphation or oxidative metabolism of paracetamol. Paracetamol clearance in females using OCS was 49% greater than in the control females. Glucuronidation and oxidative metabolism were both induced in OCS users (by 78% and 36% respectively) but sulphation was not altered. Although sex-related differences in paracetamol metabolism are unlikely to be of clinical importance, induction of paracetamol metabolism by OCS may have clinical and toxicological consequences.

Influence of sex steroids during early development on aortic 6-keto-PGF 1α synthesis in adult rats: Selective semsitivity to estrogens

Influence of sex steroids during early development on aortic 6-keto-PGF 1α synthesis in adult rats: Selective semsitivity to estrogens

Short- and long-term influences of neonatal sex steroids on α-bungarotoxin binding capacity in the mouse amygdala

Short- and long-term influences of various neonatal hormonal manipulations were assessed in the mouse amygdala with respect to α-bungarotoxin binding capacity, a possible parameter for cholinergic receptor integrity and function. To estimate the short-term effects, [ 125I]α-bungarotoxin binding to the tissue homogenate obtained from the posterior corticomedial amygdala was determined by a filtration assay using mice killed at 14 days post partum. The amygdaloid tissue from the normal male had a greater binding capacity for [ 125I]α-bungarotoxin than that from the normal female. However, castration of the male on the day of birth decreased the binding down to the female's level. A treatment of the female with either 250 μg testosterone propionate or 10 μg estradiol benzoate on days 1, 3, 5 and 7 increased the binding up to the male's level, although similar neonatal administration of 250 μg 5α-dihydrotestosterone was ineffective. The long-term effects of neonatal hormonal manipulations were examined with 77-day-old mice which had been gonadectomized for 49 days. A quantitative light-microscopic autoradiography for [ 125I]α bungarotoxin binding showed that specific grain density over the nucleus amygdaloideus medialis posterior of the androgenized female exceeded that of the female without neonatal hormone treatment. These observations provide further evidence that neonatal sex steroids play a determinate role in the sexual differentiation of the brain by exerting an organizational influence on developing cholinergic binding sites in the amygdala.

Identification and characterization of α1-adrenergic receptors in human myometrium by [ 3H]prazosin binding

α1-adrenergic receptors can be directly characterized in myometrial membranes using the specific α1-adrenergic radioligand [3H]prazosin. Compared to the previous approach, this allows a more precise determination of the α1-adrenergic receptor number and of their agonist and antagonist binding properties. Use of this radioligand might prove to be a powerful tool in distinguishing α1-receptors from the total amount of α-adrenergic receptors. As a practical application, it becomes now possible to determine whether the reported influence of sex steroid hormones on the total α-adrenergic receptor population in animal uteri does also apply to the α1-subpopulation.

Estrogen-binding sites of mammalian liver: Endocrine regulation of estrogen receptor synthesis in the regenerating rat liver

The influence of sex steroids and pituitary hormones on the synthesis of cytoplasmic estrogen receptors in fully differentiated and differentiating liver cells was studied under in vivo conditions. The liver of each animal in the study was analyzed with respect to total wet weight, protein content and estrogen receptor concentration. All three of these parameters were found to be dependent on the endocrine status of the animal. The concentration of binding sites in livers from intact and castrated males were very similar, 2590 and 2370 sites per cell, respectively. The corresponding figure for intact females in the estrus stage of the cycle was 4980 sites per livercell. Partial hepatectomy of castrated adult male rats followed by complete regeneration of the liver parenchyma for 15 days, resulted in an increase of estrogen binding sites by 64% as compared to intact males. Animals exposed to estradiol benzoate during the liver regeneration, show an increase in binding sites that exceeds the basal concentration in livers from intact male rats by 140%, and those of intact female rats by 11%. Hypophysectomy of male rats caused a reduction in binding sites to 760 sites per cell. Livers from male rats subjected to hypophysectomy and partial hepatectomy followed by complete regeneration of the parenchyma in the absence or presence of estradiol benzoate had similar levels of binding sites as those of animals subjected to hypohysectomy alone, 600 and 670 sites per liver cell, respectively. The K D values of estrogen receptor complexes in livers from animals subjected to different treatments showed only minor differences and were approximately 1.0 nanomolar. The present data indicate a multiendocrine regulation of the biosynthesis of liver estrogen binding sites that involves the gonads and pituitary. No data were obtained supporting a concept of an independent direct influence of estrogens on the synthesis of estrogen receptors in the rat liver.

The influence of a combined oral contraceptive pill and menstrual cycle phase on digital microvascular haemodynamics.

1. Nailfold capillary pressure, digital blood flow and skin temperature have been measured on days 7, 14, 21 and 28 of the menstrual cycle in 10 women on a combined oral contraceptive pill and 10 control subjects with normal menstrual cycles. 2. Capillary pressure and digital blood flow were statistically significantly higher in the group taking an oral contraceptive pill compared with control subjects. 3. Capillary pressure values for women failed to show the same positive correlation with skin temperature previously described in normal men. 4. The results are interpreted as evidence for a powerful modulating influence of sex steroids on digital microvascular haemodynamics.

Metabolic response to starvation. II. Effects of sex steroid administration to pre- and postmenopausal women

Premenopausal women become more ketotic than do men during short term starvation. The possible influence of female sex steroids on ketosis during an 84-hr fast was studied in premenopausal women receiving combined oral contraceptive steroids. The results were compared to age and weight-matched women on no steroid birth control regimen. Although concentrations of several plasma substrates, insulin, and glucagon were measured throughout the fast, no differences between groups were observed with the exception of the 36-hr interval. At this time total plasma ketones and betahydroxybutyrate were significantly higher in women receiving oral contraceptives. In a second study six postmenopausal women were investigated in a similar fashion during a 36-hr fast. The procedure was repeated following a 5-day treatment regimen of oral estradiol and medroxyprogesterone acetate. After sex steroid treatment, total plasma ketones and betahydroxybutyrate concentrations exceeded control values significantly at 36 hr while plasma alanine and free fatty acid levels were significantly lower. The results suggest that oral estrogen-progestin combinations increase the ketogenic response of pre- and postmenopausal women during the early phases of total starvation. This hormonal effect may explain, in part, why women are more sensitive to fasting than are men.

Ovarian hormones inhibit the release of prostacyclin-like material from isolated rat uterus

The influence of sex steroids on the production of prostacyclin (PGI 2) like material by the isolated rat uterus incubated in a buffer medium was explored by monitoring its ability to inhibit ADP-induced platelet aggregation. Chopped uterine strips from rats in natural estrus can generate an unstable substance that inhibits platelet aggregation and suggest to be prostacyclin. This capacity was significantly enhanced in preparations from spayed animals. The injection of 17-beta estradiol; progesterone or both diminished the production of the prostacyclin-like material by the uterus from ovariectomized rats. The already existing notion that ovarian steroids are able to regulate the synthesis of stable prostaglandins is discussed together with the present results suggesting in addition a depressive effect of sex hormones on the uterine PGI 2 synthetase system.

Influence of contraceptive and other sex steroids on aortic collagen and elastin

The effects of estradiol, progesterone, the contraceptive steroid combination mestranol-norethynodrel (M-N), and testosterone on aortic connective tissue were studied in ovariectomized and intact female rats. Estradiol and M-N administration to ovariectomized rats resulted in decreased accumulation of aortic collagen and elastin and, after injection of rats with [ 14C]proline, a lower specific activity of hydroxyproline in aortic collagen and elastin. The ratio of collagen to elastin ( C E ), which is an index of passive stiffness, was relatively low in aortas of all rats receiving female hormones and high in ovariectomized oil-treated and in testosterone-treated rats. Estradiol and M-N reduced C E mainly by decreasing the percentage collagen, but progesterone reduced it by increasing the percentage elastin. It is concluded that sex hormones differentially alter aortic collagen and elastin synthesis and degradation and in so doing alter the accumulation and proportions of the two fibers in the vessel wall.