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ABSTRACT
Vitamin D metabolites and vitamin D-binding protein (DBP) were measured in non-diabetic rats and in rats made diabetic with streptozotocin. The animals were studied in the intact state, after gonadectomy and during pregnancy. In male non-diabetic rats the serum concentrations of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and DBP decreased after orchidectomy and were restored by treatment with testosterone. In female non-diabetic rats, these parameters increased after ovariectomy. Increased 1,25-(OH)2D3 and decreased DBP concentrations were found during pregnancy in non-diabetic rats.
After the induction of diabetes in intact rats of both sexes, the concentration of DBP decreased, but a significant decrease in the concentration of 1,25-(OH)2D3 was found in male animals only. After ovariectomy, however, 1,25-(OH)2D3 decreased also in female diabetic rats.
Both orchidectomy and insulin deficiency depressed serum concentrations of 1,25-(OH)2D3 (−22 and −45% respectively) and DBP (−14 and −29% respectively), but the effects of insulin deficiency were greater than those of androgen withdrawal. Moreover, the testosterone concentration was twofold lower in intact male diabetic rats than in non-diabetic animals. Insulin, but not testosterone treatment, however, restored DBP and 1,25-(OH)2D3 concentrations in diabetic rats, and insulin was effective in intact as well as in gonadectomized animals.
This study shows that insulin deficiency decreases the concentrations of DBP and 1,25-(OH)2D3 in the rat, and that these decreases are facilitated by androgens, but counteracted by oestrogens.
J. Endocr. (1987) 115, 295–301
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A sex hormone binding globulin (SHBG) similar to human SHBG was identified in marmoset serum based on its gel electrophoretic mobility, isoelectric point and steroid binding properties. Levels of serum SHBG were measured in immature and mature males, immature females and females during the luteal phase and pregnancy; serum progesterone, 5α-dihydrotestosterone (5α-DHT), testosterone, oestradiol-17β and oestrone were also measured. Mean (± s.e.m.) concentrations of SHBG in immature males (336 ±19 nmol/l) were higher (P <0·01) than those in mature males (251 ±13 nmol/l), whereas values in the groups of females were similar (359 ± 12, 395 ± 17, 397 ± 39 nmol/l in immature, non-pregnant and pregnant females respectively). There was an inverse relationship between SHBG and the levels of testosterone (r= −0·67) and 5α-DHT (r = −0·86) in males, but the correlation was significant (P <0·05) only for 5α-DHT. There was no correlation between levels of SHBG and oestrogens in males or between levels of SHBG and any of the steroids measured in females. Equilibrium dialysis was used to assess the percentage of steroid in serum in the unbound form. Mean percentage values for unbound testosterone and 5α-DHT were lower in immature males than in mature males (P <0·01) and negatively correlated with levels of SHBG (r = −0·78, testosterone; r = −0·56, 5α-DHT).
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Instituto de Investigaciones Cerebrales, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
(Received 10 March 1978)
Injection of histamine into the third ventricle causes the release of luteinizing hormone (LH) in ovariectomized, steroid-primed and pro-oestrous rats (Donoso, Banzan & Borzino, 1976; Donoso, 1978). In oestrous rabbits, intraventricular injection of large doses of histamine or injection of histamine into the mediobasal hypothalamus induces ovulation and secretion of progesterone by the ovaries (Sawyer, 1955; Endröczi & Hilliard, 1965). However, histamine has no effect on the concentration of LH in the plasma of male rats (Donoso & Banzan, 1976). Together, these results suggest that histamine is able to induce the release of LH both before ovulation and in the presence of an adequate hormonal background.
The positive feedback effects of oestradiol and progesterone on the release of gonadotrophins are absent in male rats. Injection of oestradiol, progesterone or testosterone into steroid-primed
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. 2010 , Yeap et al . 2010 , Levinger et al . 2011 ). It has long been recognized that bone mass accrual is profoundly regulated by sex steroid hormones, which are necessary for the bone growth and for the maintenance of skeletal integrity ( Khosla
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ABSTRACT
In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment.
Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.
Journal of Endocrinology (1990) 125, 317–325
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SUMMARY
The role of ovarian hormones in the development of increased sensitivity of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) which occurs before and during the preovulatory surge of luteinizing hormone (LH) in the rat has been examined. The response of the pituitary gland was determined, with respect to the secretion of LH and follicle-stimulating hormone (FSH), after the intravenous injection of 50 ng LH-RF/100 g body weight. The LH-RF was injected 30–60 min after the administration of sodium pentobarbitone at either 13.30 h or 18.80 h of pro-oestrus. Blood samples were collected immediately before and at frequent intervals after the injection of LH-RF, and the concentration of LH and FSH in these samples was measured by radioimmunoassay.
Ovariectomy at 10.00–11.00 h of dioestrus reduced the LH response to LH-RF injected at 14.00 h of pro-oestrus, while oestradiol benzoate administered immediately after ovariectomy restored and even augmented this response. These data together with the finding that administration of the antioestrogen, ICI 46 474, at 17.00 h of dioestrus reduced the LH response to LH-RF injected on the afternoon of pro-oestrus indicates that the initial phase of increased pituitary sensitivity to LH-RF is dependent upon the marked rise in the concentration of oestradiol-17β in plasma which precedes the preovulatory surge of LH.
The abrupt, marked increase in pituitary sensitivity to LH-RF, which, in the normal cycle, occurs between 14.00 and 18.30 h of pro-oestrus, failed to develop in rats ovariectomized on the morning of dioestrus whether or not oestradiol benzoate was administered after the operation. However, the LH response to LH-RF injected on the evening of pro-oestrus increased significantly when progesterone was administered at 13.00 h of pro-oestrus in rats ovariectomized and treated with oestradiol benzoate at 10.00–11.00 h of dioestrus. This suggests that the development of the second phase of increased pituitary sensitivity to LH-RF depends, at least partially, on progesterone acting on an oestrogen-primed pituitary gland.
The concentrations of FSH in blood samples taken before injection of LH-RF at either 14.00 or 18.30 h of pro-oestrus were significantly greater in ovariectomized compared with those in sham-operated rats. In contrast the FSH responses, in terms of the mean maximal increments, were not significantly different in the various groups irrespective of the nature or time of operation or the time of injection of LH-RF. The FSH response to LH-RF was not appreciably altered by treatment with either oestradiol benzoate or progesterone immediately after ovariectomy although it was increased significantly by the sequential administration of oestrogen and progesterone. The significance of the findings that under certain conditions there were considerable differences between the LH and FSH responses to synthetic LH-RF is discussed with respect to the hypothesis that there is a common releasing factor for both gonadotrophins.
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Two experiments were performed to examine the expression of the androgen receptor (AR) gene in the pig uterus. In experiment 1, immunohistochemistry (IHC) was used to determine the distribution of the AR in uterine tIssue of pigs when collected at the first day of estrus (day 0) and the mid-luteal phase (day 12) of the estrous cycle, or early pregnancy (day 12, n=4 gilts per group). In experiment 2, AR immunostaining and AR mRNA in uterine tIssue were compared among ovariectomized gilts (n=4 per group) following treatment for 4 days with daily injections of: (1) progesterone (2 mg/kg bodyweight (BW)), (2) estradiol-17beta (E(2,) 2 micro g/kg BW), (3) E(2) plus progesterone (same dosages as 1 and 2 combined), (4) 5alpha-dihydrotestosterone (DHT, 7 micro g/kg BW), or (5) vehicle (corn oil). Data were analyzed using ANOVA. In experiment 1, nuclear staining for AR in luminal and glandular epithelia was strong and did not differ in intensity between the two locations. Immunostaining of AR in the myometrium was less (P<0.001) intense than in the luminal and glandular epithelia. Nuclei of stromal cells contained AR immunostaining that varied in intensity from strong (mainly in subepithelial stroma) to weak or no staining. Stages of the estrous cycle or early pregnancy did not influence AR immunostaining in the endometrial epithelia and myometrium. In experiment 2, immunostaining of AR in glandular and luminal epithelia and myometrium of ovariectomized gilts treated with vehicle or DHT was less (P<0.05) than in gilts treated with E(2), progesterone, or E(2) plus progesterone. Immunostaining of AR did not differ between ovariectomized gilts treated with vehicle or DHT, or between gilts treated with E(2), progesterone, or E(2) plus progesterone. In both experiments, intensity of AR immunostaining was greater in glandular epithelium located at the adluminal region compared with glandular epithelium located at the basal region of the endometrium. Competitive reverse-transcription PCR (RT-PCR) indicated a stimulatory effect (P<0.01) of E(2) on amounts of AR mRNA in whole endometrium. This increase in AR mRNA after E(2) treatment was not detected when E(2) was combined with progesterone. Endometrial AR mRNA was not influenced by DHT or progesterone relative to vehicle-treated gilts. In conclusion, immunoreactive AR is mainly present in luminal and glandular epithelia of the pig uterus and to a lesser extent in the myometrium, and does not change significantly during the estrous cycle or early pregnancy. Expression of the AR gene in the pig endometrium and myometrium appears to be regulated by E(2) and progesterone.
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The effects of neonatally administered steroids on the sensitivity of the mammary gland to tumour induction by 7,12-dimethylbenz(a)anthracene was studied as a model for delayed (de)differentiating effects of steroid hormones. Immediately after birth male and female rats were gonadectomized and treated with testosterone, oestradiol or oil. Control animals were left intact. On day 45 all the gonadectomized animals and some of the control animals received an implant which delivered continuous low levels of oestradiol. The carcinogen was administered on day 55. The administration of an oestradiol implant, which increased prolactin levels in all animals, markedly reduced tumour incidence in intact female rats and increased tumour incidence in intact male rats. Neonatal administration of testosterone or oestradiol did not significantly influence tumour incidence, histopathology or oestradiol responsiveness in neonatally gonadectomized rats but tended to decrease tumour oestradiol-receptor levels. This lack of effect of neonatal steroids in gonadectomized animals suggests that the effects observed by other authors in intact rats are mediated by changes in gonadal secretions. It is concluded that the hormonal environment during and after tumour induction plays a major role in the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas.
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Gerontology and Geriatrics, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
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). Based on these and other preclinical data, sex steroids have been suggested as strong candidates for contributing to the biological substrate influencing physical activity ( Lightfoot 2008 ). Androgens are well known for their potent anabolic actions on
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attention to the equivalence of estrus and ecdysis as fundamental reproductive events and celebrates the enduring impact of the sex steroids that control them. It also marks the centenary of the classic estrogen bioassay: the vaginal smear test for estrus
