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Abstract
The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of interleukins (ILs). It is thus reasonable to assume that inappropriate responses of the HPA axis to ILs might play a role in modulating the onset of pathological conditions such as infections. As part of our programme aimed at investigating the ability of ILs to release pro-opiomelanocortin-like peptides and corticosterone in rats exposed to alcohol, we observed that this stimulatory action appeared to be influenced by the gender of the animals. We therefore examined the ability of IL-1β, injected peripherally, to stimulate the HPA axis as a function of stage of sexual maturation and the presence or absence of circulating sex steroids.
In immature (21 to 22-day-old) rats, both males and females responded to the i.p. administration of 0·5 or 2·0 μg IL-1β/kg with statistically comparable increases in plasma ACTH levels. In contrast, females released significantly (P<0·01) more corticosterone in response to the lower dose of cytokine. Forty-day-old intact animals showed no sexual dimorphism in ACTH secretion, but the females again secreted significantly (P<0·05–0·01) more corticosterone. Gonadectomy, performed 7–8 days prior to the assay, increased the absolute amount of corticosterone released over a 60-min period. A noticeable dimorphism of the ACTH response to IL-1β became apparent in 70-day-old intact rats, with females secreting more ACTH than males. These females also released significantly more corticosterone than males under both resting and stimulated circumstances. In this age group, gonadectomy abolished the sex difference in terms of ACTH release, but augmented the total amount of corticosteroids secreted by both sexes, as well as increasing the sexual dimorphism.
These results suggest the presence of gender differences in the response of the HPA axis to IL-1β. While the sexual dimorphism of ACTH secretion appears to be dependent on circulating sex steroids, the sexually dimorphic adrenal response was retained following gonadectomy.
Journal of Endocrinology (1994) 140, 365–372
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ABSTRACT
The seasonally reproductive male little brown bat (Myotis lucifugus lucifugus) exhibits marked increases in plasma concentrations of sex steroid-binding protein (SBP) in the spring following arousal from hibernation. In this species an increase in SBP levels is induced prematurely in male bats aroused during the first half of hibernation and housed under long photoperiods; however, this rise is inhibited in bats housed under short photoperiods. In order to investigate the physiological role of the thyroid gland in the regulation of plasma SBP activity, plasma total thyroxine (T4) and SBP concentrations were determined in immature male little brown bats prematurely aroused from the first half of hibernation and maintained on either a short or long photoperiod. For this purpose a radioimmunoassay for the measurement of total T4 in bat plasma was established and validated. The results showed that immature male little brown bats aroused prematurely from hibernation and housed under a long spring-like photoperiod exhibited marked increases in plasma T4 and SBP concentrations, while animals housed under a short photoperiod showed only marginal increases in SBP, and plasma T4 remained undetectable. These results suggest that the thyroid gland, through the action of T4, may normally play an important role in the control of the post-arousal rise in plasma SBP concentrations in the little brown bat.
J. Endocr. (1986) 110, 271–278
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SUMMARY
The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of LH-RF have been examined in the female rat. Responsiveness was determined at pro-oestrus by measuring the increments in immunoreactive LH-RF of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the LH-RF response to preoptic stimulation while oestradiol benzoate (OB) or testosterone propionate (TP) administered immediately after ovariectomy significantly augmented the response. The facilitatory effect of TP was possibly due to its conversion to an aromatized derivative since 5α-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness, and, when administered to animals ovariectomized at 12.00 h of pro-oestrus, reduced the LH-RF response at 18.00 h the same day. Stimulation of the median eminence produced a significantly greater increment in LH-RF than stimulation of the preoptic area. The facilitatory action of OB on the LH-RF response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen' at the level of the preoptic area.
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, characterised by ∼400 cycles of endometrial cell proliferation, differentiation, menstrual shedding and regeneration. Although sex steroid hormones and activation of their cognate nuclear receptors are the key regulators in cyclic tissue remodelling of the
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ABSTRACT
FSH is produced and secreted from the anterior pituitary gland of rats in multiple molecular forms. At times of high gonadotrophin-releasing hormone (GnRH) and oestrogen output (e.g. the morning of the day of pro-oestrus) the pituitary increases the production of FSH isoforms with isoelectric point (pI) values >5·0, whilst sex steroid deprivation leads to the production of strongly acidic and less in-vitro biologically active FSH molecules. It is not known, however, whether sex steroids modulate the production of specific FSH isoforms by a direct action at the pituitary level or indirectly through altering the rate of synthesis and/or secretion of GnRH. In order to obtain some insight on this issue, we examined the charge heterogeneity of FSH secreted by cultured pituitary cells exposed to different FSH-releasing factors, oestradiol-17β and progesterone, alone or in different time-sequenced combinations. Anterior pituitary glands from 21-day-old female rats were enzymatically dispersed into a single cell suspension and cultured for 5 days. During days 1 to 3, cells were incubated in the absence of factors or steroid hormones; on days 3 to 4, cells were incubated in the absence (controls) or presence of either oestradiol17β (3·67 nmol/l) or oestradiol-17β plus progesterone (3·67 and 31·8 nmol/l respectively). Finally, during days 4 to 6, GnRH (10 nmol/l) or recombinant human activin-A (2 nmol/l) were added to half of all culture wells. Media from each cell group were concentrated and the several forms of secreted FSH were then separated by polyacrylamide gel isoelectric focusing (pH range 6·5–4·0) and quantitated. All media concentrates contained several forms of immunoactive secreted FSH focusing within a pH range of 6·44–4·23. A large amount (51–76%) of total FSH recovered focused within a pI range of 4·9–4·0 (area 3), whilst 20–43% and 4–8% of the total were identified within pi range of 5·9–5·0 (area 2) and 6·5–6·0 (area 1) respectively. Addition of GnRH to control or oestradiol-primed cells significantly increased the release of FSH isoforms recovered within area 2 compared with the remaining groups (per cent (±s.d.) FSH recovered within area 2 in groups treated with GnRH and those treated with oestradiol plus GnRH= 43·2±2·0 and 39·4±2·5 of total respectively; control groups and groups treated with oestradiol-17β, oestradiol-17β plus progesterone and activin-A = 32·1±1·2, 21·7±1·9, 19·7±5·0 and 21·5±4·0% of total respectively; P<0·05 compared with groups exposed to GnRH and oestradiol plus GnRH). The presence of progesterone in the culture media prevented this GnRH-mediated effect. Cells exposed to oestradiol-17β, oestradiol-17β plus progesterone and activin-A (with or without sex steroids) predominantly released FSH forms recovered within the most acidic area of the gel (area 3) (72·9±4·5, 76·6±8·6 and 70·9±5·9% of total respectively; P < 0·05 compared with GnRH-treated and oestradiol-17β plus GnRH-treated groups). There were no between-group differences in the amount of FSH recovered within area 1 (pI 5·6–6·0). FSH molecules that focused within area 2 exhibited a higher receptor-binding activity than those recovered from the most acidic region of the gel (radioreceptor assay/radioimmunoassay FSH activity ratio in area 2 = 2·56±0·29, area 3=0·83±0·03; P<0·01).
We conclude that under in-vitro conditions GnRH selectively increases the release of less acidic FSH isoforms possessing an enhanced receptor-binding potency. It is suggested that oestradiol modulates the in-vivo production and secretion of specific FSH isoforms indirectly through temporal modifications in either the rate of synthesis and/or secretion of GnRH at the hypothalamic level or pituitary responsiveness to this releasing hormone.
Journal of Endocrinology (1992) 134, 97–106
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.e. originate from the uterus and act on the ovary), acting only at the site of their production ( Narumiya et al . 1999 ). The presence and regulation of EPs and FP receptors were found to be regulated by sex steroids in the mouse ( Yang et al . 1997 ) and
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programmed by neonatal testosterone Manipulation of sex steroid hormones during critical perinatal periods can masculinize or feminize the HPA axis. Male rats treated with the antiandrogen flutamide from gestational day 13 to PD 20 show changes in the
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ABSTRACT
Inhibin bioactivity and mRNA for inhibin subunits were measured in four dog Sertoli cell tumours and in the testes of five normal control dogs. The tumours contained increased levels of inhibin (P <0·05) and mRNA for the α and βB subunits when compared with controls, whereas the mRNA for the βA subunit was not detected in tumours or control testes. The inhibin bioactivity was associated with a 32 kDa molecule in both Sertoli cell tumours and normal dog testes; no higher molecular weight forms were found after sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
Peripheral levels of immunoassayable inhibin in dogs with Sertoli cell tumours were higher than those in the controls (P = 0·01), indicating that it might be possible to use this parameter as a marker for Sertoli cell tumours. Other testicular tumours, however, might also secrete immunoactive inhibin. The increased inhibin concentrations are likely to be the cause of the suppressed peripheral levels of FSH (P <0·02). However, peripheral levels of LH (P <0·02) and testosterone (P <0·01) were also suppressed in the dogs with Sertoli cell tumours, whereas the concentrations of oestradiol in the peripheral plasma of both groups did not differ. Finally, i.v. injection of the LHRH agonist buserelin caused a significant increase in LH and testosterone in the control dogs, but not in the dogs with Sertoli cell tumours.
It was concluded that secretory products from the Sertoli cell tumours suppressed pituitary gonadotrophin secretion. It is unlikely that testosterone or oestradiol play a role in this respect. FSH may be suppressed by the high levels of inhibin in tumour-bearing dogs, but it remains unclear whether inhibin or another Sertoli cell product is responsible for the unresponsiveness of the pituitary gland to LHRH and the suppression of LH.
Journal of Endocrinology (1990) 127, 235–242
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ABSTRACT
Androgenized, oestrogenized and control female and male rats were used to establish possible differences in the alteration of the prolactin control system. Neonatal treatment involved administration of oestradiol benzoate or testosterone propionate (TP) on days 1 and 5 to the males and on day 5 to the females. Oil-treated animals were used as controls. Plasma prolactin levels were measured in these animals during adulthood (a) before gonadectomy, performed on day 80, and 27 days after gonadectomy and (b) on the 2 days (at 10.00 and 17.00 h) after administration of a single dose of TP to gonadectomized animals. Oestrogenized rats had the highest plasma prolactin concentrations just before and after gonadectomy. Testosterone propionate increased plasma prolactin levels in all groups. This response was more notable in the female than in the male groups, and was highest in the oestrogenized animals. Temporal rhythms of the prolactin response to TP were daily, perhaps circadian, with increased levels in the afternoon compared with those in the morning. This pattern was not present in oestrogenized females and androgenized males. Results suggest (a) that oestrogens and androgens given neonatally differ in their ability to alter the prolactin control system, and (b) that females seem to be more sensitive than males to changes in hypothalamic differentiation induced by neonatal steroid treatment.
J. Endocr. (1985) 105, 429–433
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SUMMARY
The purpose of these experiments was to compare the behavioural and morphological effects of exogenous sex hormones in gonadectomized quail (Coturnix coturnix japonica) with those in quail having regressed gonads as a result of exposure to short days. In Expt 1, male quail were assigned to one of three treatment groups: (1) intact, exposed to 16 h light:8 h darkness and injected with oil (group 16L); (2) gonadectomized, exposed to 16 h light:8 h darkness and injected with 2·5 mg testosterone propionate (TP)/day (group 16Lcastrated); and (3) intact, exposed to 8 h light:16 h darkness, and injected with 2·5 mg TP/day (group 8L). Groups 16L-castrated and 8L responded similarly to testosterone, copulating with equal frequency and rapidity after the same number of days of treatment, and also developing proctodeal (foam) glands of a similar size. Only on day 7 of testosterone treatment did the results for these two groups differ. By day 14, the behaviour of both groups resembled that of the 16L birds.
In Expt 2 female quail were assigned to the same three treatment groups, except that the hormone treatment was 25 μg oestradiol benzoate/day. Group 8L became sexually receptive sooner than the 16L-ovariectomized quail, but by day 13 both groups had oviducts of similar size, were equally receptive, and were as receptive as the 16L females.
The results suggest that the effects of photoperiod on sexual behaviour in this species are mediated largely, if not wholly, by the gonads. They also suggest that exposure to short days and surgical gonadectomy are rather similar experimental procedures in the quail.
