bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal (hpg) mice
Authors: McDowell I. F. W. , Morris J. F. , Charlton H. M. , Fink G. 
Published: December 2008

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH); consequently the pituitary gonadotrophs, though differentiated, remain inactive. The acute and chronic responses of gonadotrophs in hpg mice to LH-RH were studied using quantitative electron microscopy, immunocytochemistry for LH and radioimmunoassay of the gonadotrophins.
Acute i.v. administration of 40 ng LH-RH to male hpg mice produced an eightfold increase in plasma LH after 5 min, but granule depletion was not detectable ultrastructurally. Vacuoles (300–600 nm) were present more frequently in gonadotrophs from hpg mice given LH-RH compared with control mice. Daily s.c. administration of 2 μg LH-RH to male hpg mice for 20 days stimulated a 63-fold increase in the pituitary content of FSH but only a twofold increase in the pituitary content of LH. Testicular weight increased fivefold but the weight of the seminal vesicles did not change. The frequency of cells immunoreactive for LH increased (× 1·6), the gonadotrophs hypertrophied (× 1·9) and the cell content of granules increased (× 2·3) to values close to the normal range. The rough endoplasmic reticulum and Golgi apparatus became more prominent. A striking result of long-term daily administration of LH-RH was the accumulation of large (1–2 μm) lipid droplets in about 40% of gonadotrophs. All these changes induced by LH-RH regressed towards the untreated hpg state when LH-RH administration was discontinued for 5 and 10 days. These results show that the gonadotrophs of hpg mice can be stimulated trophically by LH-RH, and that long-term administration stimulates the synthesis and release of the gonadotrophins but the effect on FSH is much greater than on LH.
Growth of the endometrium and cotyledons during pregnancy in the ewe: rates of protein secretion and synthesis and nuclear and cytosol steroid hormone receptor levels
Authors: Miller B. G. , Tassell R. , Stone G. M. 
Published: December 2008

The time-course of cell hypertrophy and changes in in-vitro rates of secretion and synthesis of protein in intercaruncular and caruncular endometrium and maternal and fetal cotyledonary placenta have been examined during days 0–112 of pregnancy in the ewe. The concentrations of high-affinity receptors for oestradiol and progesterone in nuclear and cytosol fractions from these tissues were also determined.
Protein secretion by intercaruncular endometrium increased 25-fold between days 0 and 84. On day 84 10−5 m-colchicine blocked 75% of total secretion. Protein secretion did not increase in the other tissues. Protein synthesis and RNA: DNA ratio in intercaruncular endometrium increased steadily between days 0 and 112, whereas they did not change in caruncular endometrium between days 0 and 28 and declined in cotyledon between days 56 and 112. The levels of cytosol receptor for oestradiol and progesterone and of nuclear receptor for oestradiol in all tissues during days 56–112 were very low in relation to the corresponding levels in caruncular endometrium on day 0. The level of nuclear progesterone receptor in caruncular endometrium increased threefold between oestrus and day 28. The level of this receptor in cotyledon remained low on days 56–112, but in intercaruncular endometrium it increased to high values on days 84–112.
The results demonstrated a major surge in secretory activity by the intercaruncular endometrium at around mid-gestation, which was associated with a marked increase in nuclear progesterone receptor levels but only a low level of nuclear oestradiol receptor. The observations do not suggest any important role for oestradiol or progesterone in the growth of fetal and maternal cotyledon.
Effect of underfeeding upon the rate of milk ejection in the lactating rat
Authors: Grosvenor C. E. , Mena F. 
Published: December 2008

Lactating rats were fed at a level equivalent to 75% of the daily food consumed by controls, which had food available ad libitum, from days 4–14 or from days 4–12 post partum. The underfed mothers lost about 10% of their initial weight whereas control mothers gained weight slightly during this time. The litters (six pups) of underfed mothers gained 20% less weight than those of controls but remained healthy. The milk obtained by the pups from six glands (the remaining six glands had been ligated on day 3) during a timed suckling, plus that subsequently obtained after oxytocin injections to the mother, totalled 7·4± 0·80 g in underfed and 15± 0·62 g in control mothers on day 14, and 6 ± 0·41 g in underfed compared with 8 ±0·50 g in control mothers on day 12. The pups of underfed mothers obtained a significantly greater percentage of the total milk after 10 (30 v. 6%), 15 (84 v. 32%) and 45 (100 v. 57%) min of suckling than did those of control mothers. In two trials for the milk ejection test, the litters of control and underfed mothers were exchanged. The pups of control mothers suckled by underfed mothers in both trials obtained a significantly greater percentage of the total milk (64%) in 15 min than did the pups of underfed mothers suckled by control mothers (25%).
Oxytocin-induced intramammary pressure (IMP) responses recorded under urethane anaesthesia achieved a greater amplitude in underfed than in control mothers in response to each dose (0·4, 0·8 and 1·6 mu.) of oxytocin administered intravenously. The average slope of the dose–response curve was 1·25 cm H2O/0·1 mu. oxytocin compared with 0·75cm H2O/0·1 mu. for fed mothers. The amplitude of the IMP in response to a 1·6 mu. dose of oxytocin also was greater in underfed mothers over a range of volumes of milk added incrementally to empty glands. The difference was most striking at low volumes of milk (0·2–0·6 ml) within the gland. The data from these experiments suggest the more rapid transfer of milk from mother to pups in underfed rats is due at least in part to adaptations within the mammary gland, possibly involving reductions in the sympathetic-mediated tone of mammary ducts.
Cyproheptadine and desmethylcyproheptadine directly inhibit the release of adrenocorticotrophin and β-lipotrophin/β-endorphin activity from the neurointermediate lobe of the rat pituitary gland
Authors: Lamberts S. W. J. , Bons E. G. , Uitterlinden P. , Hackeng W. H. 
Published: December 2008

Cyproheptadine and its metabolite desmethylcyproheptadine were shown to suppress directly the release of adrenocorticotrophin (ACTH) and β-lipotrophin/β-endorphin activity from the neurointermediate lobe of the pituitary gland incubated in vitro. Neither compound affected the release of ACTH from the anterior pituitary gland. Serotonin stimulated the release of ACTH and β-lipotrophin/β-endorphin activity from the neurointermediate lobe, but did not influence the (desmethyl)cyproheptadine-mediated inhibition of hormone release.
These results indicate that serotonin and cyproheptadine affect hormone release by the neurointermediate lobe by a direct action. The effect of cyproheptadine, however, might not be exerted by a serotonin receptor.
Regulation of luteal activity in adult female rats treated neonatally with testosterone propionate
Authors: van der Schoot P. , de Greef W. J. 
Published: December 2008

The present study was concerned with the control of luteal activity in female rats which had been treated neonatally with 1·25 mg testosterone propionate (TP). Treatment of such rats in adulthood with 15 i.u. human chorionic gonadotrophin induced ovulation followed by a period of luteal activity. The two daily surges of prolactin secretion, typical for a period of luteal activity in the normal female rat, were not observed in TP-treated females. Instead, higher basal levels of prolactin were observed in TP-treated females than in normal female rats. Furthermore, uterine traumatization at 5 days after ovulation did not result in the formation of decidual tissue.
In intact TP-treated females luteal activity, induced and temporarily sustained by an ectopic pituitary transplant, persisted after removal of the pituitary graft. In contrast, in TP-treated females which had been ovariectomized on day 25 of age and had received an ovarian transplant before induction of the luteal phase, luteal activity ended within a week after removal of the ectopic pituitary gland. Females treated with TP which had been ovariectomized on day 25 of life had lower plasma levels of prolactin and higher levels of dopamine in hypophysial stalk plasma than intact TP-treated females when measured at 4 months of age. Treatment of ovariectomized rats with oestradiol-17β increased levels of prolactin in plasma and lowered levels of dopamine in hypophysial stalk plasma.
It is concluded that the control of luteal activity in TP-treated females shows 'male' characteristics. However, the presence of the ovaries in such rats leads to decreased hypothalamic release of dopamine and increased plasma levels of prolactin, probably due to increased oestrogen levels. These increased levels of prolactin are sufficient to maintain luteal activity.
Effects of parathyroid hormone and the synthetic 1–34 amino-terminal fragment in rats and dogs
Authors: Stevenson R. W. , Parsons J. A. 
Published: December 2008

Since the structural requirements for all known biological activities of parathyroid hormone (PTH(1–84)) are virtually satisfied by the amino-terminal 34 amino acid fragment, PTH(1–34), we investigated whether this fragment could elaborate the overall actions of the intact hormone in the whole animal by comparing the effects of equimolar infusions of each peptide to dogs and rats. Infusion of bovine PTH(1–84) (bPTH(1–84)) at 17 pmol/kg per h for 20 h to three dogs or at 100 and 200 pmol/kg per h to groups of six rats for 5 days produced greater hypercalcaemia (3·02±0·03, 2·52±0·07 and 3·24±0·11 mmol/l respectively) than equimolar infusions of human PTH(1–34) (hPTH(1–34)) (2·61±0·03, 2·46 ± 0·05 and 2·71 ±0·09 mmol/l respectively). A significant calcium rise was not observed in dogs until after 4 h of PTH infusion. No rise in plasma calcium was apparent in rats, however, until the third day of PTH infusion. Only in parathyroidectomized rats was there a rise in plasma calcium within 24 h of starting an infusion of PTH. The hypercalciuria and plasma phosphate responses in dogs during equimolar infusions of hPTH(1–34) and bPTH(1–84) were not significantly different. However, by day 5 of infusion in rats greater hypercalciuria was produced by bPTH(1–84). Although infusion of hPTH(1–34) and bPTH(1–84) caused rises in urinary cyclic AMP excretion (measured only in the dog) of immediate onset and equal magnitude, bPTH(1–84) tended to produce greater phosphaturia than hPTH(1–34) in both species. If the assumption is correct that the half-lives of hPTH(1–34) and bPTH(1–84) in the circulation are similar and provided that hPTH does not inherently have less biological activity than bPTH, then during equimolar infusions of these peptides into dogs and rats, the greater responses observed with bPTH(1–84) suggest that intact PTH may have a direct action of its own in vivo before being metabolized into smaller biologically active fragments.
In additional experiments using parathyroidectomized rats, the infusion rate of bPTH(1–84) required to restore normocalcaemia was 26 pmol/kg per h. Although near-normal calcaemia and intestinal calcium absorption could still be maintained when the infusion rate was increased to 39 pmol/kg per h, hypercalciuria and phosphaturia became apparent.
Mammary gland lactose, plasma progesterone and lactogenesis in the marsupial Macropus eugenii
Authors: Findlay Leigh , Ward K. L. , Renfree M. B. 
Published: December 2008

Mammary gland lactose concentrations in pregnant tammar wallabies remained low at 115 ± (s.e.m.) μg/g wet weight of tissue until immediately before parturition, then increased to 1274±262 μg/g after birth. Concentrations in non-pregnant cyclic animals were generally low 143±36 μg/g), but were raised in three animals around the time of oestrus.
Removal of the corpus luteum on day 18 of pregnancy or the oestrous cycle caused an increase in lactose concentrations in both lutectomized and sham-operated animals. This occurred despite a significant lowering of peripheral plasma progesterone concentration in only the lutectomized group. Plasma cortisol concentrations were high in some of these animals, but showed no consistent relationships with the raised lactose concentrations.
The increased peripartum lactose concentration normally coincides with a sharp fall in peripheral plasma progesterone concentration, but artificial maintenance of high progesterone levels had no effect on the increase of mammary gland lactose at parturition.
Mammary gland lactose concentrations in tammar wallabies are therefore a useful indicator of biosynthetic activity and as an index of lactogenesis but the role, if any, of progesterone withdrawal in lactogenesis remains unclear.
Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives
Authors: Di Carlo Francesco , Gallo Elena , Conti Giuseppe , Racca Silvia 
Published: December 2008

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol–receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time.
The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.
Effects of tamoxifen on concentrations of luteinizing hormone and follicle-stimulating hormone in the plasma of ovariectomized ewes
Authors: Clarke I. J. 
Published: December 2008

The effects of tamoxifen on peripheral plasma concentrations of gonadotrophins were studied in ovariectomized ewes. First, ovariectomized ewes were injected (i.m.) with 10 mg tamoxifen citrate/day for 4 days which caused a significant reduction in plasma LH concentrations within 4 days and plasma FSH concentrations within 1 day of the commencement of treatment. Further groups of ovariectomized ewes were then injected (i.m.) with two injections of 10 mg tamoxifen citrate 6 h apart or 20 μg oestradiol benzoate (OB) or tamoxifen citrate plus OB or oil. Tamoxifen treatment caused a reduction in plasma LH and FSH concentrations within 6 h. In four of our ewes receiving OB, a surge in LH secretion was observed; a similar response was observed in two out of four ewes given the combination of tamoxifen citrate and OB. No LH surge was seen in ovariectomized ewes given tamoxifen alone.
These results show that tamoxifen reduces plasma gonadotrophin levels in ovariectomized ewes suggesting it is an oestrogen agonist in the sheep pituitary gland. A partial oestrogen antagonist action of tamoxifen is similarly suggested by its ability to block the oestrogen-induced LH surge in some ovariectomized ewes. Since tamoxifen consistently lowers plasma gonadotrophin levels in ovariectomized ewes this could result from action via oestrogen receptors or by central nervous system, non-oestrogen receptor-mediated effects.
Effect of nigericin and varying potassium concentrations on the prolactin-stimulated synthesis of milk fat in explants of mammary alveolar tissue from rabbits
Authors: Smith J. V. , Falconer I. R. 
Published: December 2008

The possible role of K+ as a 'second messenger' for prolactin was investigated. Explants obtained from mammary glands of pseudopregnant rabbits were cultured (a) in media with varying potassium concentrations and (b) in the presence of the potassium-specific ionophore, nigericin. The explants were examined histologically and the rate of protein synthesis was measured to determine the viability of the tissue. Increase in the rate of fatty acid synthesis in the presence of prolactin was used as a marker of prolactin stimulation.
At low K+ concentrations prolactin-stimulated fatty acid synthesis decreased with the decrease in K+ concentration of the media, whereas there was no similar trend in the rate of protein synthesis. Nigericin (0·01–0·1 μmol/l) inhibited fatty acid synthesis and protein synthesis in the presence or absence of prolactin without significantly affecting tissue K+ content. The mechanism of nigericin inhibition is hence unclear and the results do not provide support for K+ as a 'second messenger' for prolactin.
Stimulation of sodium transport by toad skin incubated with natural derivatives of corticosterone and deoxycorticosterone
Authors: Beauwens Renaud , Birmingham Marion , Crabbé Jean 
Published: December 2008

The effects on sodium transport of several steroids physiologically secreted or possibly involved in pathological disorders were compared with those of aldosterone in the isolated toad skin.
The 18-hydroxylated derivatives of deoxycorticosterone and corticosterone, in contrast to their parent compounds, significantly enhanced sodium transport at a concentration of 50 nmol/l. In the presence of glucose, 18-hydroxydeoxycorticosterone increased trans-epithelial potential difference, as did aldosterone. The 19-nor derivative of deoxycorticosterone, recently implicated in the aetiology of adrenal regeneration hypertension, stimulated sodium transport, unlike 19-nor-corticosterone and 16-oxo-androstenediol. Insulin significantly increased sodium transport in aldosterone-treated skin and lowered the resistance. The natriferic response to vasopressin was potentiated fivefold by exposure of the skin to aldosterone and was doubled in skin exposed to 19-nor-deoxycorticosterone.
We conclude that 18-hydroxylated adrenocortical steroids can play a physiological role in salt retention; furthermore, these steroids, as well as 19-nor-deoxycorticosterone, could be involved in pathological conditions such as low renin hypertension. Caution should be exercised in evaluating mineralocorticoid potency solely in terms of the urinary sodium to potassium ratio.
Stability of the human nuclear oestrogen receptor: influence of temperature and ionic strength
Authors: Love C. A. , Cowan S. K. , Laing L. M. , Leake R. E. 
Published: December 2008

The measurement of oestrogen receptors in the nuclei of cells of human breast cancer is becoming increasingly important for patient management. However, the steroid-binding properties of the oestrogen nuclear receptor of human cells under different conditions of temperature and ionic strength have received little attention despite the relevance of the receptor for interpretation of assay data. This paper reports a study on the influence of temperature and ionic strength on the exchange rate of [3H]oestradiol from human breast and endometrial nuclear receptor.
When the oestrogen–nuclear receptor complex was bound to intact or sheared nuclei, the displacement of bound [3H]oestradiol into buffer containing excess unlabelled oestradiol increased with temperature but was significant over 24 h even at 4 °C for nuclei from both breast and endometrium. The use of protease inhibitors combined with relabelling of nuclear receptor after incubation confirmed that the observations at 4 °C represented exchange of hormone rather than degradation of the hormone–receptor complex. Degradation was seen at higher temperatures.
Measurement of the on-rate of [3H]oestradiol onto nuclear receptor prefilled with unlabelled oestradiol showed that on-rate was also significant over 24 h at 4 °C The displacement of oestradiol from salt-extracted, hydroxylapatite-precipitated receptor also increased with temperature although, in this case, no displacement could be detected until temperatures above 4 °C were reached.
Only 40% of total oestrogen receptor detectable in intact human nuclei was solubilized by the standard method of salt extraction in 0·6 mol KC1/1. As the salt concentration was raised (0–0·6 mol KC1/1), an increase in the stripping of oestradiol from the hormone–receptor complex was observed. Such stripping of nuclear receptor during salt extraction would lead to a false impression of the proportion of 'empty' nuclear receptors.
The results show that filled oestrogen nuclear receptor from human tumour tissue may be assayed by exchange at 4 °C over 24 h. This eliminates the protease degradation of receptor which occurs at higher assay temperatures.
Alterations in ovarian steroid and gonadotrophin secretion preceding the cessation of regular oestrous cycles in ageing female rats
Authors: Nass T. E. , LaPolt P. S. , Judd H. L. , Lu J. K. H. 
Published: December 2008

ABSTRACT
To determine whether discernible alterations in neuroendocrine and/or ovarian function precede the loss of regular oestrous cycles in ageing female rats, the present study examined the pattern of gonadotrophin secretion near the time of ovulation and the pattern of ovarian steroid secretion in the early morning of prooestrus in middle-aged (10–12 months old) females displaying regular oestrous cycles and compared these with young (4 months old) animals. In addition, the subsequent reproductive patterns in these animals were observed and correlations between the changes in hormonal profiles and the decline in regular reproductive cyclicity were established. In middle-aged females which subsequently ceased to display regular oestrous cycles (middle-aged non-regular; M-NR) within 1–2 months, the pro-oestrous surge of LH was significantly reduced in magnitude. There was no difference in the LH surge between young females and middle-aged animals which maintained regular oestrous cycles (middle-aged regular; M-R) for at least 2 months. There also was no difference in the magnitude of the pro-oestrous FSH surge or in the secondary rise in FSH in the early morning of oestrus among young, M-R and M-NR females. In a separate group of middle-aged females which subsequently became M-NR, serum concentrations of both oestradiol and testosterone in the early morning of pro-oestrus were markedly raised over those in the young and M-R groups. We suggest that an earlier rise in circulating oestradiol and testosterone concentrations in middle-aged females over many consecutive regular oestrous cycles may gradually render the central nervous system less responsive to the stimulatory feedback effects of ovarian steroids on LH release. As a consequence, the pattern of the pro-oestrous LH surge may be progressively altered in ageing rats until it is inadequate for regular ovulatory function.
J. Endocr. (1984) 100, 43–50