bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey
Authors: Lunn S. F. , Cowen G. M. , Morris K. D. , Fraser H. M.
Published: December 2008

In a previous study pituitary-testicular function was shown to be maintained in a New World primate after the administration of an LHRH agonist implant. In the present study the mechanism of action of the same LHRH agonist (buserelin) on pituitary–gonadal function in the marmoset was investigated and a comparison made between the effects of treatment in three intact males, six adult cyclic females with regular ovulatory cycles, and six long-term ovariectomized animals. These were injected s.c. with an LHRH agonist implant (1·5 mg buserelin in a rod 0·5 cm long). In both the males and intact females, basal plasma LH concentrations were maintained within the normal range throughout the expected duration of agonist action (at least 3 months). Despite this, an absence of response to an LHRH challenge indicated that pituitary desensitization had occurred. In the intact females, ovulation was inhibited in five of six animals, plasma progesterone concentrations initially being maintained but subsequently remaining suppressed until 136 ± 18 (s.e.m.) days after treatment. Responsiveness to administered LHRH returned prior to onset of return to ovarian cycles. In contrast, in ovariectomized marmosets, plasma LH was markedly suppressed to concentrations which were at or below the limit of detection of the assay and were therefore less than those observed in the buserelin-implanted intact animals.

These results show that apparently normal pituitary-gonadal function in this species disguises an underlying pituitary desensitization to LHRH. This allows continuation of testosterone secretion in the male, but in the female ovulation is prevented, presumably as a result of failure of the desensitized pituitary to produce an LH surge. Since LH concentrations in buserelin-implanted ovariectomized animals were suppressed to levels less than those seen in the treated animal, the maintenance of basal LH secretion may be the result of a protective influence of gonadal factors.

Journal of Endocrinology (1992) 132, 217–224
Production of parathyroid hormone-related protein by the mammary gland of the goat
Authors: Ratcliffe W. A. , Thompson G. E. , Caret A. D. , Peaker M.
Published: December 2008

Parathyroid hormone-related protein (PTHRP) has been quantified by sensitive specific immunoassays in mammary venous blood and milk from 7 days before to 7 days after parturition in the goat. A significant venousarterial concentration gradient in plasma PTHRP 1–86 concentrations was demonstrated across the mammary gland, indicating that PTHRP enters the maternal circulation and may have a role in calcium homoeostasis during lactation. Significant and sustained increases in mammary venous and milk PTHRP 1–86 concentrations were found from 1 day before parturition to 7 days afterwards, with peak concentrations of 1·57 ± 0·58 pmol/l (plasma) and 8·69 ±2·95 nmol/l (milk) (mean ± s.e.m.) occurring on day −1 and the day of parturition respectively. Estimates of the mammary output of PTHRP into plasma in four goats averaged 9% (range 1–25%) of that secreted into milk. Suppression of maternal prolactin concentrations by bromocriptine significantly reduced milk yield and the mammary venous PTHRP concentration, without affecting the concentration of PTHRP in milk. In conclusion, parturition in the goat is associated with a sustained increase in secretion of PTHRP into both plasma and milk; the former may be involved in maternal calcium homoeostasis, whereas the latter may have a role in the neonate.

Journal of Endocrinology (1992) 133, 87–93
Effects of insulin-like growth factor-I and insulin on the in-vitro uptake of sulphate by eel branchial cartilage: evidence for the presence of independent hepatic and pancreatic sulphation factors
Authors: Duan C. , Hirano T.
Published: December 2008

The possible roles of insulin-like growth factor-I (IGF-I) and insulin in regulating cartilage growth were studied in the teleost Anguilla japonica. Significant sulphation activity was found in the extracts of pancreas, liver and muscle, but not in those of kidney, intestine or spleen. The hepatic sulphation activity was significantly decreased by hypophysectomy or by fasting for 14 days, suggesting that this activity is regulated by pituitary function and nutritional status. Northern blot analysis revealed that the hepatic IGF-I mRNA in the eel consists of a major 4·0 kb band. This mRNA was GH-dependent and was significantly decreased by fasting for 14 days.

On the other hand, fasting for 14 days had no significant effect on pancreatic sulphation activity. Pancreatic extracts from both intact and hypophysectomized eels exhibited equally significant stimulating activity. Addition of bovine or human insulin (1–250 ng/ml) to the culture medium significantly stimulated sulphate uptake in a dose-dependent manner. Teleost (coho salmon) insulin was as effective as bovine insulin. Bovine insulin was more effective than IGF-I at lower concentrations (1–4 ng/ml) but less effective at higher concentrations (10–250 ng/ml). These results indicate that not only IGF-I but also insulin are likely to be involved in the regulation of cartilage growth in the eel.

Journal of Endocrinology (1992) 133, 211–219
Effect of growth hormone and insulin-like growth factor-I on DNA synthesis and matrix production in rat epiphyseal chondrocytes in monolayer culture
Authors: Ohlsson C. , Nilsson A. , Isaksson O. G. P. , Lindahl A.
Published: December 2008

The influence of various culture conditions was studied on the effect of GH and insulin-like growth factor-I (IGF-I) on DNA and matrix synthesis in epiphyseal rat chondrocytes in monolayer culture.

Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in 48-well culture plates and precultured for 10 days in Ham's F-12 medium supplemented with 1% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture, the medium was changed to Ham's F-12 medium supplemented with 1% serum from hypophysectomized rats, and the effect of GH and IGF-I on DNA synthesis ([3H]thymidine incorporation) and matrix production ([35S]sulphate uptake) was studied during an additional 96-h culture period. Isotopes were present during the last 24 h of culture.

Both hGH and IGF-I stimulated DNA synthesis in a dose-dependent manner. A maximal effect of GH was seen at a concentration of 25 μg/l (60 ± 11% stimulation over control) and for IGF-I at 10 μg/l (162 ± 12%). The stimulatory effects of the same concentrations of human GH (hGH) and IGF-I on [35S]sulphate uptake were 135 ± 25 and 320 ± 42% respectively. In-vitro pulse labelling revealed that GH did not produce a response during the first 3 days of culture (after addition of GH) but was effective during days 4 and 5 of culture. In contrast, IGF-I was effective throughout the culture period. Pretreatment of cells with GH or IGF-I for 2·5 days showed that GH but not IGF-I produced a sustained effect on [3H]thymidine uptake.

In order to study the influence of cell density on the effect of GH and IGF-I on DNA synthesis, the effect of added peptides was evaluated after different preculture periods (5–15 days). A maximal stimulatory effect of hGH was seen at a cell density of 150 000–300 000 cells/cm2. GH had no significant effect at a low (< 100 000 cells/cm2) or a high (>400 000 cells/cm2) cell density. The magnitude of the stimulatory effect of IGF-I was the same at densities between 10 000 and 250 000 cells/cm2, but was reduced at higher cell densities (over 250 000 cells/cm2).

Chondrogenic properties of cells that had been cultured for 15 days were verified in vitro by positive alcian blue staining and identification of type II collagen, and in vivo by development of cartilage nodules in nude mice.

The results from the present study clearly show that GH and IGF-I both stimulate DNA synthesis and matrix production in epiphyseal chondrocytes in monolayer culture. The results also demonstrate that expression of the effect of GH is highly dependent upon the culture conditions.

Journal of Endocrinology (1992) 133, 291–300
Control of protein and matrix-molecule synthesis in isolated ovine fetal growth-plate chondrocytes by the interactions of basic fibroblast growth factor, insulin-like growth factors-I and -II, insulin and transforming growth factor-β1
Authors: Hill D. J. , Logan A. , McGarry M. , De Sousa D.
Published: December 2008

Chondrogenesis is thought to be controlled by interactions between circulating anabolic hormones and locally produced peptide growth factors, and involves ordered changes in matrix composition which ultimately allow endochondral calcification. We have used a model of isolated ovine fetal growth-plate chondrocytes to examine the actions and interactions of basic fibroblast growth factor (basic FGF), insulin-like growth factors-I and -II (IGF-I and -II), insulin and transforming growth factor-β1 (TGF-β1) on total protein, collagen or non-collagenous protein and sulphated glycosaminoglycan synthesis. These parameters were determined by assessment of the incorporation by monolayer cultures of early passage chondrocytes of [3H]leucine, [14C]proline and [35S]sulphate respectively, followed by partial molecular characterization. Basic FGF enhanced total protein synthesis with a half-maximal effective concentration of 270 ± 60 pmol/l (mean ± s.e.m., four animals) and was sixfold more active on a molar basis than IGF-I or insulin, and 28-fold more active that IGF-II which is the endogenously synthesized IGF. The actions of basic FGF were additive to those of IGF-I or insulin. More detailed analysis of extracellular-matrix component synthesis showed that basic FGF, IGF-I and insulin each caused significant increases in the synthesis of collagen and sulphated glycosaminoglycans. TGF-β1 had no effect on total protein synthesis by chondrocytes when present alone at concentrations of 200 pmol/l or less, but was inhibitory at 400 pmol/l. However, the use of this parameter masked a stimulatory action of 50 or 100 pmol TGF-β1 on sulphated glycosaminoglycan synthesis and a relative shift in the ratio of collagen: non-collagenous protein synthesis in favour of the former. A synergistic interaction existed between TGF-β1 (20–100 pmol/l) and basic FGF which potentiated total protein and collagen synthesis, and their actions on sulphated glycosaminoglycan production were additive. The same concentrations of TGF-β1 inhibited the ability of IGF-I or insulin to stimulate total protein or collagen synthesis, but were additive to their stimulatory effects on sulphated glycosaminoglycan synthesis. The results suggest that matrix-molecule composition and the anabolic status of the epiphyseal growth-plate may be modulated in utero by multiple interactions between peptide growth factors produced locally, such as basic FGF, IGF-II and TGF-β1, and circulating hormones such as insulin and IGF-I.

Journal of Endocrinology (1992) 133, 363–373
Preovulatory follicle development and luteal function in ewes immunized against a synthetic peptide sequence of the α subunit of bovine inhibin
Authors: McLeod B. J. , Hunter M. G. , Bleach E. C. L. , Glencross R. G. , Wrathall J. H. M.
Published: December 2008

Immunization against inhibin consistently results in an increase in ovulation rate in sheep, but the effects that this treatment has on follicle development are unknown. In order to determine the influence of inhibin, parameters of follicle development were assessed in ewes that had been actively immunized against a synthetic peptide homologous to the N-terminal sequence (α1–29, Tyr30) of the a subunit of bovine inhibin, a treatment that neutralizes the biological activity of endogenous inhibin. The final stages of preovulatory follicle development that culminate in ovulation were induced in seasonally anoestrous ewes, and follicles were recovered prior to the predicted time of ovulation. After priming with progestagen, inhibin-immunized and control ewes were treated with gonadotrophin-releasing hormone (GnRH) by continuous infusion (200 ng/h). The ovaries were recovered at slaughter 24 h after the start of GnRH treatment and all follicles ≥ 2·0 mm diameter were dissected out and their capacity to produce oestradiol in vitro was assessed. Further groups of similarly treated animals were blood-sampled daily to determine luteal function following GnRH-induced ovulation. The ovaries were recovered from these ewes at slaughter 10 days after the start of GnRH treatment, the corpora lutea were dissected out and their progesterone content was assessed.

There were more (P < 0·01) follicles of 5–6 mm diameter (3·2 ± 0·45 (s.e.m.) compared with 1·1 ± 0·25 follicles/ewe) and more (P < 0·001) follicles of > 6 mm diameter (2·8 ± 0·56 compared with 0·9 ± 0·17 follicles/ewe) in inhibin-immunized than in control ewes. In addition, the mean number of the antral follicles that were oestrogenic was greater (P < 0·05) in immunized than in control ewes (2·8 ± 0·66 compared with 1·3 ± 0·25 follicles/ewe).

In animals slaughtered 10 days after the start of GnRH treatment, mean ovulation rate was greater (3·17 ± 0·65 and 1·14 ± 0·14, P < 0·01) in inhibin-immunized ewes. Although there was more (P < 0·01) total luteal tissue/ewe in the immunized group, both the mean weight and progesterone content (ng/mg tissue) of individual corpora lutea were similar between treatment groups. Mean plasma progesterone levels increased earlier and reached higher (P < 0·01) mean concentrations in immunized than in control ewes.

These results demonstrate that immunization against inhibin increases the number of preovulatory follicles during the follicular phase, and that steroidogenesis within these follicles and the resultant corpora lutea appears to be normal.

Journal of Endocrinology (1992) 133, 413–419
Growth hormone treatment increases oestrogen receptor concentration in the guinea-pig uterus
Authors: Bezecný I. , Bártová J. , Škarda J.
Published: December 2008

Growth hormone does not act as a body growthpromoting hormone during the postnatal period in the guinea-pig. To determine whether it affects uterine and mammary growth, guinea-pigs of 8–9 weeks of age were treated with either recombinant bovine GH (bGH; 0·5 mg per animal) or vehicle for 10 days. Uterine and mammary weights were not changed by treating the animals with bGH. The amount of available cytosolic oestradiol receptor per unit of uterine weight or DNA content, or in whole uteri was increased in bGH-treated animals 7·3 to 14·0-fold) when compared with controls. The nuclear uterine oestradiol receptor concentration was 3·3- to 6·7-fold higher than in controls. The dissociation constant values did not differ between control and bGHtreated animals, suggesting that uterine oestradiol receptors are regulated by GH through changes in the number of binding sites rather than alteration of their binding affinity. Mammary growth and oestradiol receptor levels were unaffected by bGH treatment.

The results of this investigation demonstrate that injected bGH selectively affects the oestradiol receptor level in guinea-pig uterine tissue.

Journal of Endocrinology (1992) 134, 5–9
Antiprogesterone RU486 increases serum immunoreactive inhibin levels and LH:FSH and testosterone:oestradiol ratios in cyclic rats
Authors: Sánchez-Criado J. E. , Uilenbroek J. Th. J. , de Jong F. H.
Published: December 2008

Since administration of the antiprogesterone RU486 to cyclic rats results in a dissociation of basal LH and FSH secretion we studied its effects on peripheral levels of inhibin, oestradiol and testosterone throughout the oestrous cycle. Cyclic rats were given RU486 (2 mg) twice daily (09.00 and 17.00 h) on metoestrus, dioestrus and pro-oestrus. Oil-treated rats were used as controls.

Serum concentrations of immunoreactive inhibin in oil-treated rats increased from metoestrus to prooestrus and decreased at oestrus. RU486-treated rats had serum inhibin concentrations significantly increased over oil-treated rats at dioestrus and prooestrus, but not at oestrus. At both pro-oestrus and oestrus serum concentrations of LH, testosterone and oestradiol were significantly raised in RU486-treated rats compared with oil-treated controls. In contrast, serum FSH concentrations in RU486-treated rats were decreased on both days. Ovaries from RU486-treated rats showed an increased testosterone content at pro-oestrus, mainly in the interstitial tissue.

The results of thepresent study demonstrate that RU486 has a stimulatory effect on inhibin secretion, and offer an explanation for the decrease in basal serum FSH levels. The low FSH secretion on the morning of oestrus in spite of the low levels of inhibin suggests that progesterone is involved in FSH secretion at this time.

Journal of Endocrinology (1992) 134, 51–57
Epidermal growth factor stimulates production of insulin-like growth factor-binding protein-1 in human granulosa-luteal cells
Authors: Angervo M. , Koistinen R. , Seppälä M.
Published: December 2008

Insulin-like growth factor-I (IGF-I) enhances and epidermal growth factor (EGF) inhibits gonadotrophin-induced aromatization in granulosa cells. Our previous studies have shown that human ovarian granulosa cells synthesize insulin-like growth factor-binding protein-1 (IGFBP-1) which inhibits IGF-stimulated DNA synthesis. The present study addresses the effect of EGF and gonadotrophins in the regulation of IGFBP-1 release by human granulosa cells cultured in serum-free medium. At concentrations of 1–100 μg/l EGF was found to stimulate IGFBP-1 secretion. This was not due to cell proliferation, as the viable cell count remained unaffected. Growth hormone and gonadotrophins had no effect on IGFBP-1 secretion when added alone to culture medium. These results suggest that EGF regulates IGFBP-1 secretion in human granulosa-luteal cells.

Journal of Endocrinology (1992) 134, 127–131
Influence of lactotroph cell density on prolactin secretion in rats
Authors: Pasolli H. A. , Torres A. I. , Aoki A.
Published: December 2008

The relationships between the stimulation of prolactin secretion and proliferation of lactotrophs was studied from a multidisciplinary standpoint in three experimental models. Administration of both oestrogen and sulpiride resulted in a significant increase in prolactin secretion and in the lactotroph population. A single injection of 10 μg oestradiol benzoate (OB) induced a twofold increase in the proliferation of lactotrophs (morphometrically as volume density), which increased further (2·5-fold) after three OB injections. Parallel changes were observed in the net counts made on lactotrophs sectioned through the nucleus to avoid possible distortions in volume density caused by hypertrophic cytoplasms. Comparable results were obtained with the mitotic index in the same groups of rats exposed to treatment with colchicine. The effect of sulpiride on proliferation of lactotrophs was also significant (1·7-fold) but less pronounced than in rats treated with oestrogens. The treatments with oestrogen and sulpiride did not stimulate lactotrophic activity in a similar way, as judged by the levels of serum prolactin and the storage patterns of small and big prolactin in pituitary glands. Serum prolactin (mean ± s.e.m.) in control ovariectomized rats was 4·0±0·9 μg/l and one and three injections of OB raised these levels to 14·4±5·0 and 28·8±4·6 μg/l respectively. The highest levels of serum prolactin were seen in sulpiride-treated rats (467·2±28·7 μg/l). Striking differences occurred in the pituitary contents of big prolactin, the control values increasing from 5·3±0·5 to 10·2±1·3 μg/mg after one OB injection and to 14· 7 ±0·7 μg/mg after three OB injections. In contrast, the concentration of big prolactin in sulpiride-treated rats was very low (1·85 ± 0·2 μg/mg), 2·8-times smaller than the controls. Other changes were also found in the small prolactin content in pituitary tissue with higher values in all the experimental models. These differences could only be detected after differential extraction of big and small molecular forms of prolactin.

In ovariectomized rats, treatment with several doses of oestrogen enhanced the proliferation observed in the lactotroph population and increased the number of mitoses. In turn, morphological data could be closely related to the higher levels of prolactin in serum and pituitary glands. A sustained stimulation of lactotrophic secretion was always followed by proliferation of lactotrophs, the number of which fluctuated in parallel with the degree of stimulation.

Journal of Endocrinology (1992) 134, 241–246
Hypothalamic-pituitary function in neonatally oestrogen-treated male rats
Authors: Pinilla L. , Garnelo P. , Gaytan F. , Aguilar E.
Published: December 2008

Neonatal oestrogen administration to male rats permanently impaired the function of the pituitary-testicular axis possibly by inhibiting neonatal gonadotrophin secretion. To analyse the hypothalamus and/or pituitary involvement in this inhibition, pituitary responsiveness to acute stimulation with LH-releasing hormone (LHRH) was studied in vivo and in vitro in Wistar male rats injected on day 1 of age with oestradiol benzoate (OB) or olive oil. FSH and LH pituitary content and plasma concentrations were reduced in oestrogenized male rats at days 10 and 16 of age. Likewise, the in-vivo increase in gonadotrophin plasma concentrations after acute stimulation with LHRH was almost completely suppressed in 10-and 16-day-old oestrogenized males. In vitro, the increased secretion of FSH after LHRH stimulation was abolished and the LH response strongly reduced in pituitaries from oestrogenized males. Finally, the effects of neonatal oestrogenization were not abolished by treatment from day 1 to day 15 with an LHRH agonist (0·01 μg/kg per 12 h). We conclude that in male rats the effects of oestrogenization are due to both a reduction in LHRH endogenous secretion and a decrease in the pituitary responsiveness to LHRH.

Journal of Endocrinology (1992) 134, 279–286
Receptor binding and growth-promoting activity of insulin-like growth factor-I in a bovine mammary epithelial cell line (MAC-T3)
Authors: Zhao X. , McBride B. W. , Politis I. , Huynh H. T. , Akers R. M. , Burton J. H. , Turner J. D.
Published: December 2008

Insulin-like growth factor-I (IGF-I) has been known to be mitogenic to a variety of cell types, although a growth-regulatory role for IGF-I on bovine mammary epithelial cells has not been fully investigated. In the present study, we examined the receptor binding of IGF-I and its effect on growth in a bovine mammary epithelial cell line (MAC-T3). Specific receptors for IGF-I were detected on cultured bovine mammary epithelial cells. Competitive binding revealed that half-maximal inhibition of 125I-labelled IGF-I binding by IGF-I was approximately 3 μg/l. Dissociation rate constant of the IGF-I receptor was 3·10±0·06 nmol/l (s.e.m.) with a receptor site concentration of 366 ± 8 fmol/mg protein for the average of three experiments. IGF-I exerted a positive mitogenic effect on MAC-T3 cells according to both direct DNA assay and thymidine incorporation assay. Moreover, the mitogenic effect of IGF-I on MAC-T3 cells was enhanced by the addition of fetal calf serum in the culture media. The present results suggest that the bovine mammary epithelial cell line (MAC-T3) provides a useful model system with which to study the biological actions of insulin-like growth factors on the bovine mammary secretory tissue in vitro.

Journal of Endocrinology (1992) 134, 307–312
Effect of the antiprogestin RU486 on uterine sensitivity to oxytocin in ewes in late pregnancy
Authors: Burgess K. M. , Jenkin G. , Ralph M. M. , Thorburn G. D.
Published: December 2008

The effect of RU486, a synthetic progesterone receptor antagonist, on basal uterine prostaglandin (PG) release and release in response to oxytocin injection has been investigated in late-pregnant sheep (days 135–140 of gestation). Fifteen hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4), bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals. Uteroovarian vein concentrations of 13,14-dihydro-15-keto PGF2α (PGFM) and PGE2 were determined before and during oxytocin stimulation. Basal concentrations of both PGFM and PGE2 were significantly (P < 0·001) increased in ewes 15 h after RU486 administration compared with ewes receiving vehicle alone. Concentrations of PGFM, but not PGE2, increased significantly (P < 0·001) following injection of each dose of oxytocin in both treated and untreated animals. The response to oxytocin, measured both as the area under the curve and as the peak height of PGFM release, was significantly (P <0·05) greater in RU486-treated ewes. There was no significant effect of oxytocin on the area or peak height of PGE2 response in either RU486-treated or control animals. These results demonstrate that treatment of late-pregnant ewes with RU486 results in an increase in basal uterine PGFM and PGE2 as well as oxytocin-stimulated PGFM release.

Journal of Endocrinology (1992) 134, 353–360
Regulation of female brain aromatase activity during the reproductive cycle of the dove
Authors: Hutchison R. E. , Wozniak A. W. , Hutchison J. B.
Published: December 2008

Oestrogen is formed in the female dove brain. The aim of this study was to determine whether (a) the catalytic properties of the brain aromatase are similar to the ovarian enzyme and (b) aromatase activity in the female brain changes during the reproductive cycle and is influenced by steroids and environmental stimuli.

The results show that female preoptic aromatase has a higher substrate affinity than the enzyme in ovarian follicles (apparent Km: preoptic area, 7 nmol/l; ovarian follicles, 29 nmol/l), but a lower activity in the preoptic area (Vmax: preoptic area, 290 fmol/mg tissue per h; ovarian follicles, 843 fmol/mg tissue per h). In intact females with developing follicles, oestradiol-17β formation was higher in the posterior hypothalamus than the preoptic area. Females in a later stage of reproductive development (yolked follicles) had a different distribution of oestrogen formation with increased aromatase activity in the preoptic area. Preoptic and posterior hypothalamic aromatase activity of females paired with males for 10 days was positively correlated (r = 0·84, P = 0·0001; r = 0·75, P = 0·001 respectively) with ovarian development. Females with undeveloped ovaries which interacted with males had higher preoptic aromatase activity than visually isolated females with similar ovarian development, suggesting that behavioural stimuli have direct effects on brain aromatase activity which are independent of the ovary. Oestradiol benzoate treatment increased preoptic and posterior hypothalamic aromatase activity in intact and ovariectomized females, and testosterone propionate treatment increased anterior hypothalamic aromatase activity, but did not affect other areas, indicating that the distribution of induced aromatase activity is steroid-specific. Oestrogen treatment in ovariectomized or intact females did not replicate the maximal hypothalamic aromatase activity seen when the ovary contained yolked follicles.

We conclude that brain aromatase activity is related directly to ovarian condition during the reproductive cycle of the female dove. As in the male, steroids have a role in the regulation of oestrogen formation in the female hypothalamus; behavioural stimuli are also likely to be involved in the control of the brain enzyme.

Journal of Endocrinology (1992) 134, 385–396
Sex hormone concentrations in blood serum from the North Atlantic fin whale (Balaenoptera physalus)
Authors: Kjeld J. M. , Sigurjónsson J. , Árnason A.
Published: December 2008

Blood serum concentrations of testosterone and progesterone were measured in postmortem samples taken at sea from 814 fin whales (Balaenoptera physalus) caught during the summers (June–September) of 1981–1989. The ages of 781 of these animals were also assessed. The testosterone concentrations in samples from 352 males averaged 2 nmol/l; 41 samples had concentrations of 0·1 nmol/l or lower and 34 of these came from whales aged between 2 and 14 years and showed a Gaussian type of age distribution with a peak number at 7 to 8 years. The mean testosterone concentrations in the males increased by more than fourfold between June and August. Serum progesterone concentrations of the 462 females fell into three separate groups: (1) group I with values ≤ 0·1 nmol/l; (2) group II with intermediate values of > 0·1 nmol/l but <10 nmol/l; (3) group III with values of ≥ 10 nmol/l. These three groups of females seemed to consist respectively of young sexually immature females, mature non-pregnant females and pregnant females. The age distribution in the groups indicated that puberty in females is attained chiefly between the ages of 7 and 10. The yearly pregnancy rate (that percentage of all females caught and studied in a year which had progesterone values ≥10 nmol/l) was between 35% and 55%, except in 1987 when it was 67%. The yearly pregnancy rate would range from 56% to 93% if only mature females (i.e. those with serum progesterone >0·1 nmol/l) were considered. Serum oestradiol concentrations in male and female fin whales had no relation to age, sex or pregnancy.

Journal of Endocrinology (1992) 134, 405–413
Oestrogen enhancement of the myometrial response to exogenous parathyroid hormone-related protein (PTHrP), and tissue localization of endogenous PTHrP and its mRNA in the virgin rat uterus
Authors: Paspaliaris V. , Vargas S. J. , Gillespie M. T. , Williams E. D. , Danks J.A. , Moseley J. M. , Story M. E. , Pennefather J. N. , Leaver D. D. , Martin T. J.
Published: December 2008

Classical pharmacological studies have shown that oestrogen dominance in humans and other animals can increase the responsiveness of the uterus to many locally acting peptides. Parathyroid hormone-related protein (PTHrP) has been shown to be expressed in the pregnant and non-pregnant rat uterus and exogenous PTHrP is known to relax uterine contraction in vitro. We investigated whether oestrogen dominance can influence the responsiveness of the uterine horn to PTHrP, and further studied the localization of PTHrP mRNA and protein in the rat uterine horn using in-situ hybridization and immunohistochemistry. Exogenous PTHrP(1–34) inhibited spontaneous and electrically induced contractions in uteri isolated from non-cycling rats. Pretreatment of non-cycling rats with oestradiol-17β increased uterine sensitivity to PTHrP: EC50 values for inhibition of spontaneous contractions by PTHrP were 0·33 nmol/l, 1·1 nmol/l, 2·6 nmol/l and 7800 nmol/l in uteri from animals treated for 2 days with oestradiol-17β alone, 2 days with oestradiol-17β+1 day progesterone, 1 day with oestradiol-17β alone and in untreated rats respectively. Similar EC50 values were obtained for electrically stimulated uteri. In agreement with these findings, uterine horns from cycling rats in pro-oestrous and oestrous phases of the cycle showed a higher responsiveness to PTHrP(1–34) when compared with uterine horns taken from rats in metoestrus and dioestrus. PTHrP mRNA and protein were detected in the endometrial epithelium lining of the lumen and the endometrial glands, as well as in the myometrium of rats which were either pretreated for 2 days with oestradiol-17β or untreated. This study suggests that PTHrP may act in an autocrine and/or paracrine manner to modulate uterine motility and function.

Journal of Endocrinology (1992) 134, 415–425
Suramin affects differentiated and undifferentiated human thyroid epithelial cells in vitro
Authors: Trieb K. , Dorfinger K. , Neuhold N. , Selzer E. , Wilfing A. , Czernin S. , Hermann M. , Niederle B. , Gessl A. , Vierhapper H. , Freissmuth M. , Grubeck-Loebenstein B.
Published: December 2008

In the last decade, suramin has become known for its antiproliferative, differentiation-inducing effects on cells and has been successfully used in the therapy of cancer patients. The present study was undertaken to investigate the effects of suramin on normal human thyroid cells in primary monolayer culture and to analyse whether it also affected cells from thyroid carcinomas. The results show that suramin, at concentrations similar to serum levels obtainable during therapy, inhibited the proliferation of thyroid cells as well as the secretion of thyroglobulin. It suppressed the activation of adenylyl cyclase in thyroid membranes and decreased the immunogenicity of the cells by reducing their surface expression of HLA-DR and ICAM-1. Although the morphology of differentiated thyroid cells remained unaffected by suramin, morphological changes compatible with differentiation were observed in cells from undifferentiated thyroid carcinomas when suramin was added to the culture medium. In conclusion, the data demonstrate that suramin has pronounced in-vitro effects on normal and neoplastic thyroid cells. It may, therefore, also be effective in patients with thyroid cancer, for whom no other form of treatment is available.

Journal of Endocrinology (1992) 134, 505–511
Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth hormone response to growth hormone-releasing hormone
Authors: Trainer P. J. , Kirk J. M. W. , Savage M. O. , Grossman A. B. , Besser G. M.
Published: December 2008

The GH response to insulin-induced hypoglycaemia and growth hormone-releasing hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an anticholinesterase that stimulates GH secretion, probably by inhibition of hypothalamic somatostatin secretion. This work was designed to study the site of action of glucocorticoids in inhibiting the secretion of GH.

Eight healthy male volunteers were studied on three occasions in random order. They took 2 mg oral dexamethasone or placebo at precisely 6-hourly intervals for 48 h before receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH (100 μg) i.v. Samples for measuring GH were obtained at 15 min intervals for 2 h.

The 'area under the curve' (AUC) for each of the treatments was significantly different: dexamethasone–pyridostigmine–GHRH (mean ± s.e.m., 1938 ± 631 mU/min per 1), dexamethasone–placebo–GHRH (634 ±211) and placebo–placebo–GHRH (4267 ± 1183) (P<0·02, Wilcoxon test).

In conclusion, dexamethasone given for 48 h significantly inhibited the AUC for GH following treatment with GHRH. However, pretreatment with pyridostigmine significantly reversed the inhibition although this was still partial. Our data suggested that this short-term suppressive effect of dexamethasone was independent of GHRH, and most probably relates to stimulation of the release of somatostatin.

Journal of Endocrinology (1992) 134, 513–517
Influence of ovarian steroids on myometrial sensitivity and tolerance to relaxin in the rat in vivo: lack of cross-tolerance between relaxin, salbutamol and cromakalim
Authors: Downing S. J. , Hollingsworth M.
Published: December 2008

The influence of oestradiol benzoate and progesterone on uterine sensitivity and development of tolerance to relaxin was investigated in bilaterally ovariectomized non-pregnant rats in vivo. Bolus doses of relaxin (2–20 μg/kg i.v.) produced rapid and reversible inhibition of uterine contractions in a dose-dependent manner. Treatment with oestradiol benzoate or oestradiol benzoate plus progesterone significantly increased uterine sensitivity to relaxin over 48 h by 2·4- to 8·5-fold. Tolerance to relaxin developed during continuous infusion of the hormone at 20 μg/kg per h for 40 h. A 7·8- to 17·4-fold reduction in sensitivity to relaxin was observed in relaxin-infused rats, whereas no change in sensitivity was observed in saline-infused rats. Infusion of relaxin at 50 μg/kg per h for 40 h produced a 131·8-fold reduction in uterine sensitivity to relaxin. The uterus remained tolerant to relaxin for up to 24 h after cessation of infusion. Treatment with oestradiol benzoate and/or progesterone did not influence the extent of tolerance development, but a more rapid recovery of uterine sensitivity to relaxin was observed in rats treated with oestradiol benzoate plus progesterone. Cross-tolerance with other uterine relaxant drugs was measured to investigate possible common mechanisms of action and sites of tolerance between relaxin and a β-adrenoceptor agonist (salbutamol) and potassium channel openers (cromakalim and minoxidil sulphate). No cross-tolerance was observed between relaxin and salbutamol, or relaxin and cromakalim or minoxidil sulphate. Cross-tolerance between cromakalim and minoxidil sulphate was seen.

Journal of Endocrinology (1992) 135, 17–28
Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat
Authors: Fink G. , Dow R. C. , Casley D. , Johnston C. I. , Bennie J. , Carroll S. , Dick H.
Published: December 2008

The role of atrial natriuretic peptide (ANP) in the ACTH response to stress and the glucocorticoid negative feedback control of ACTH release was investigated in adult male homozygous Brattleboro and adrenalectomized Wistar rats respectively, using the technique of immunoneutralization. The relatively low ACTH response to stress and the lack of arginine vasopressin make the homozygous Brattleboro rat a more rigorous and simpler preparation in which to test the hypothesis that ANP is involved in the ACTH response to stress. In both sets of experiments, blood sampling and injection of sheep anti-ANP or control serum were carried out in conscious animals through intra-atrial cannulae implanted 2 days previously under halothane anaesthesia. A 30-s exposure to ether resulted in a brisk twofold increase in the plasma ACTH concentrations in homozygous Brattleboro rats infused with anti-ANP, but not control serum. The injection of either dexamethasone, a potent glucocorticoid receptor agonist, or corticosterone resulted in a rapid and marked reduction in the plasma concentrations of ACTH in Wistar rats which had been adrenalectomized, under halothane anaesthesia, at least 21 days before experimentation. The inhibitory action of dexamethasone, but not corticosterone, was significantly reduced in animals infused with anti-ANP serum.

These results show that the inhibition of ANP release into hypophysial portal blood is probably important for triggering the ACTH response to stress and that ANP may play a role in corticosteroid negative feedback control of ACTH release mediated by type II (glucocorticoid) receptors.

Journal of Endocrinology (1992) 135, 37–43
Relationship between the resting metabolic rate and hepatic metabolism in rats: effect of hyperthyroidism and fasting for 24 hours
Authors: Iossa S. , Liverini G. , Barletta A.
Published: December 2008

We have examined the relationship between the changes in resting metabolic rate (RMR) and those in hepatic metabolism induced by hyperthyroidism and fasting for 24 h. We found that hyperthyroidism induced a significant increase in RMR, while fasting for 24 h reduced RMR in euthyroid but not in hyperthyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hyperthyroid rats, fed or fasted for 24 h. Hyperthyroidism induced an increase in oxygen consumption in rat liver cells; fasting for 24 h increased respiratory rates in isolated liver cells from euthyroid but not from hyperthyroid rats.

The findings showed that hyperthyroidism and fasting for 24 h have opposite effects on RMR but similar effects on hepatic metabolism. The results also indicated that the increase in RMR found in hyperthyroid rats is partly due to an increase in hepatic metabolism, while no correlation exists between variations in resting and hepatic metabolism induced by 24-h fasting.

Journal of Endocrinology (1992) 135, 45–51
Salivary insulin-like growth factor-I originates from local synthesis
Authors: Ryan J. , Mantle T. , McQuaid S. , Costigan D. C.
Published: December 2008

Insulin-like growth factor-I (IGF-I) is a GH-dependent growth factor found in its highest concentrations in plasma. It is also measurable in saliva. The origins of salivary IGF-I concentrations were studied. Intracardial administration of Sprague–Dawley rats with 125I-labelled IGF-I and subsequent analysis of plasma and saliva samples by exclusion gel chromatography and SDS-PAGE, followed by autoradiography, demonstrated the apparent inability of IGF-I to cross from the plasma pool through to saliva. 125I-Labelled IGF-I was not chromatographed immediately before injection, resulting in administration of free iodide along with the iodinated peptide. This free iodide was demonstrable in saliva, indicating that movement of substances from plasma to saliva was measurable using the levels of 125I activity administered. Free iodide in saliva was not contributed to by 125I-labelled IGF-I degradation since 125I-labelled IGF-I was shown to be stable in saliva over 24 h. These data indicated that IGF-I in saliva is produced locally. Identification of a 4·7 kb IGF-I mRNA transcript in rat parotid salivary gland was consistent with IGF-I synthesis within that tissue.

Journal of Endocrinology (1992) 135, 85–90
Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney
Authors: Kageyama Y. , Suzuki H. , Saruta T.
Published: December 2008

It has been suggested that the mineralocorticoid action of glycyrrhizin is caused by a defect in the conversion of cortisol to cortisone through inhibition of the enzyme 11β-dehydrogenase (11β-DH). We investigated the functional significance of the inhibition of this enzyme as a mechanism of the mineralocorticoid action of glycyrrhizin. Eighteen healthy volunteers were divided into three groups of six and treated as follows: (1) 225 mg glycyrrhizin/day, (2) 0·1 mg 9α-fluorocortisol (FC)/day and (3) 225 mg glycyrrhizin and 1·5 mg dexamethasone/day, all of which were given for 7 days. The administration of glycyrrhizin or FC induced a similar mineralocorticoid effect; specifically, suppression of plasma renin activity, hypokalaemia and kaliuresis. During the concomitant administration of glycyrrhizin and dexamethasone, however, these mineralocorticoid effects were significantly attenuated. During the administration of glycyrrhizin, urinary excretion of cortisol increased without change in the plasma levels of cortisol, while both plasma level and urinary excretion of cortisone decreased. Changes in cortisol metabolism were not observed during the administration of FC. These results demonstrated the functional significance of the inhibition of 11β-DH in the mineralocorticoid activity of glycyrrhizin in man.

Journal of Endocrinology (1992) 135, 147–152
The role of growth hormone, prolactin and insulin-like growth factors in the regulation of rat mammary gland and adipose tissue metabolism during lactation
Authors: Barber M. C. , Clegg R. A. , Finley E. , Vernon R. G. , Flint D. J.
Published: December 2008

Inhibition of prolactin secretion with bromocriptine and neutralization of GH action with a specific antiserum to rat GH (rGH) were used to explore the modes of action of GH and prolactin in maintaining lactation in the rat. Treatment of dams with anti-rGH caused a small reduction in litter weight gain whilst bromocriptine reduced litter weight gain by 50%. When both treatments were combined, however, milk yield ceased completely and this wasaccompanied by a wide variety of effects on mammary lipid metabolism including decreases in the mRNA concentrations of acetyl CoA carboxylase, fatty acid synthase, malic enzyme and lipoprotein lipase. Activities of acetyl CoA carboxylase and lipoprotein lipase were also significantly reduced. Reciprocal changes were evident in adipose tissue with increases in acetyl CoA carboxylase and lipoprotein lipase activities. In conjunction with a decreased lipolytic response to noradrenaline in adipose tissue of animals given the combined treatment of bromocriptine and anti-rGH, this represented a co-ordinated series of changes to reduce lipid synthesis in the mammary gland and enhance lipogenesis and triglyceride storage in adipose tissue as milk production ceased. All of these effects could be prevented in part by concurrent treatment with GH, but insulin-like growth factor-I (IGF-I) and IGF-II failed to affect any of the parameters measured. Taken as a whole, these data suggest that (1) both prolactin and GH induce a co-ordinated series of changes in the mammary gland, (2) the intracellular controls involved clearly operate at the level of gene transcription although post-translational controls are also probably involved, (3) the effects of GH on the mammary gland could not be mimicked by IGFs and (4) although GH clearly regulates lipid metabolism in adipose tissue in a manner which should favour nutrient utilization by the mammary gland, these effects are probably too small to account for the effects of GH on milk production. Since GH receptors have not been reported to be present on mammary secretory cells, the precise mode of action of GH remains uncertain.

Journal of Endocrinology (1992) 135, 195–202
In-vivo regulation of messenger RNA encoding insulin-like growth factor-I (IGF-I) and its receptor by diabetes, insulin and IGF-I in rat muscle
Authors: Bornfeldt K. E. , Skottner A. , Arnqvist H. J.
Published: December 2008

The effects of continuous or acute administration of insulin or insulin-like growth factor-I (IGF-I) on IGF-I mRNA and IGF-I receptor mRNA were studied in the skeletal muscle (gastrocnemius), heart muscle and vascular smooth muscle (aorta) of non-diabetic and diabetic rats using a solution hybridization assay. The levels of IGF-I mRNA in the different types of muscle markedly decreased by diabetes, whereas changes in IGF-I receptor mRNA were less consistent. Continuous infusion of diabetic rats with insulin (28 or 35 nmol/day) for 4 days normalized the altered levels of IGF-I mRNA and IGF-1 receptor mRNA. Infusion of equimolar concentrations of IGF-I did not affect IGF-I mRNA, but decreased the level of IGF-I receptor mRNA in skeletal muscle.

In acute experiments, rats were injected with equipotent blood glucose-lowering doses of insulin (14 nmol) or IGF-I (107 nmol). Insulin did not significantly affect levels of IGF-I mRNA, but decreased levels of IGF-I receptor mRNA in skeletal muscle and aorta. IGF-I increased levels of IGF-I mRNA in heart muscle, and markedly decreased levels of IGF-I receptor mRNA in skeletal muscle and heart muscle from non-diabetic and diabetic rats.

In conclusion, exogenous IGF-I and insulin can increase IGF-I mRNA and decrease IGF-I receptor mRNA, indicating that both insulin and IGF-I can act as regulators of the IGF-I system in muscle in vivo.

Journal of Endocrinology (1992) 135, 203–211
Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages
Authors: Costa Rosa L. F. B. P. , Cury Y. , Curi R.
Published: December 2008

In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormonetreated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism..

Journal of Endocrinology (1992) 135, 213–219