bluuebunny/crossref_metadata_2025 huggingface dataset:
RENAL RESPONSE TO INFUSION OF ISOTONIC RINGER-LOCKE SOLUTION: EFFECT OF HYPOPHYSECTOMY
Authors: BAKER J. T. , SOLOMON S.
Published: December 2008

A comparison of the renal response to extracellular fluid volume expansion (5% body weight) was made between 25 normal and 25 chronically hypophysectomized rats. The extracellular fluid compartments averaged 25 ± 1% of body weight in both groups during control, fasted conditions. Extracellular fluid volume increased to 33 ± 1% in hypophysectomized and 34 ± 2% in normal rats during expansion, based on body weight. In addition, filtration fraction was similar in both normal and hypophysectomized rats during control (0·29 ± 0·03 and 0·26 ± 0·02 respectively) and infusion of Ringer–Locke solution (0·24 ± 0·05 and 0·27 ± 0·05 respectively). Thus our results cannot be explained by differences in the degree of expansion or failure to increase filtration in proportion to plasma flow. During infusion of isotonic Ringer–Locke solution, fractional water and sodium excretion both averaged 5·1% in normal rats and only 1·3% and 0·82% respectively in hypophysectomized rats. The ratio of single nephron to whole kidney filtration rate failed to increase as much in hypophysectomized compared with normal rats. Significant increases of fractional volume excretion occurred in both groups by the end of the accessible portion of the proximal tubule. However, fractional water reabsorption was depressed significantly more in normal (mean = 37%) than in hypophysectomized rats (mean = 19%). Fractional water reabsorption in distal tubules was similar in both groups during expansion. Arterial pressure was lower in hypophysectomized rats under control conditions, but showed similar changes during expansion compared with normal rats. Passage time decreased significantly in all groups after Ringer–Locke infusion, but remained prolonged in hypophysectomized rats in proximal and distal tubules. It is concluded that chronic hypophysectomy results in a less efficient renal excretion of volume and sodium chloride load. This inefficiency appears to be related in part to (1) failure of the proximal tubule to depress water reabsorption to a level equivalent to normal rats, and (2) failure to re-distribute flow to outer cortical glomeruli following extracellular fluid volume expansion in hypophysectomized rats.
AN ASSAY FOR PLASMA SOMATOMEDIN: [3H]THYMIDINE INCORPORATION BY ISOLATED RABBIT CHONDROCYTES
Authors: ASHTON I. K. , FRANCIS M. J. O.
Published: December 2008

The incorporation of [3H]thymidine by rabbit chondrocytes in vitro has been developed as a sensitive assay for plasma somatomedin. A concentration of normal plasma of 2·5% enhanced [3H]thymidine incorporation by 5- to 20-fold compared with basal levels in the absence of plasma. The mean potency of plasma from normal adult men was 0·96 ± 0·1 u./ml (mean ± s.d.) and from acromegalic patients 1·9 ± 0·4 u./ml. The apparent potency of hypopituitary plasma alone increased on heating which suggested the presence of heatlabile inhibitors of somatomedin activity. The potency of heated hypopituitary plasma (0·6 ± 0·09 u./ml) remained significantly lower (P < 0·01) than normal plasma. Human growth hormone (0·1–20 μu./ml), bovine growth hormone (0·5–20 μu./ml), insulin (0·5–5 μu./ml) and glucose (0·3–2 mmol/l) had no direct effect on the incorporation of [3H]thymidine. Chondrocytes which had been previously stored frozen also showed a response to plasma somatomedin.
STEROIDOGENESIS IN ISOLATED RAT ADRENAL GLOMERULOSA CELLS: RESPONSE TO PHYSIOLOGICAL CONCENTRATIONS OF ANGIOTENSIN II AND EFFECTS OF POTASSIUM, SEROTONIN AND [Sar1,Ala8]-ANGIOTENSIN II
Authors: BING R. F. , SCHULSTER D.
Published: December 2008

Zona glomerulosa cell suspensions with less than 5% fasciculata-reticularis cell contamination were prepared by collagenase digestion of normal rat adrenal capsular tissue. The corticosterone and aldosterone content of such cell suspensions under various conditions were measured simultaneously. Increases in steroid production were observed with physiological concentrations of angiotensin 11 (2 × 10−11 mol/l), with sigmoid log dose-response curves for both corticosterone and aldosterone production (ED50:4 × 10−10 and 8 × 10−10 mol angiotensin II/l respectively). The response to angiotensin II could be abolished by [Sar1, Ala8]-angiotensin II; 50% inhibition was produced by an equimolar concentration of this antagonist. Extracellular potassium ion concentration was shown to affect steroid output dramatically, confirming previous observations and underlining its importance as a physiological regulator of aldosterone secretion. The characteristics of the effect of serotonin, a potent stimulator of steroidogenesis in this system, were also observed. Differences in the maximal responses to angiotensin II and serotonin could not be explained by degradation and probably reflect their different modes of action.

Zona fasciculata-reticularis cell suspensions were prepared in a similar fashion from decapsulated adrenal glands, and showed no increase in steroid production with those concentrations of angiotensin II (2 × 10−11 to 2 × 10−7 mol/l) that stimulated glomerulosa cells. However, angiotensin II amide did increase corticosterone production in isolated fasciculata-reticularis cells at concentrations greater than 2 × 10−5mol/l, as reported by others, whereas angiotensin free acid did not.

It is concluded that this sensitive rat glomerulosa cell suspension will be useful for studying the modes of action of angiotensin II and other stimulators of aldosterone biosynthesis.
GONADOTROPHIN RELEASE BY A HIGHLY ACTIVE ANALOGUE OF LUTEINIZING HORMONE RELEASING HORMONE IN RATS IMMUNIZED AGAINST LUTEINIZING HORMONE RELEASING HORMONE
Authors: FRASER H. M. , SANDOW J.
Published: December 2008

Immunization against luteinizing hormone releasing hormone (LH-RH) in adult male rats produced a progressive decline in LH and FSH in the circulation to low or non-detectable levels. d-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide is an analogue of LH-RH having highly active LH-RH properties in the normal rat. Because it is also immunologically different from LH-RH it can stimulate gonadotrophin release from the anterior pituitary gland of rats immunized against LH-RH without interference from the antibody. The analogue stimulated LH and FSH release in rats 15 weeks after immunization against LH-RH when antibody titre was highest, and after long-term (35 weeks) immunization against LH-RH. d-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide and related analogues are therefore potentially useful for reversing the effects of immunization against LH-RH.
FUNCTIONAL ACTIVITY OF THE HYPOTHALAMO-PITUITARY COMPLEX IN THE RAT AFTER BETAMETHASONE TREATMENT
Authors: BUCKINGHAM JULIA C. , HODGES J. R.
Published: December 2008

The precise nature of the impairment of hypothalamo-pituitary-adrenocortical (HPA) activity which follows prolonged corticosteroid treatment is not yet understood. To study this problem, hypothalamic corticotrophin releasing hormone (CRH) content, pituitary ACTH content and the functional capacity of adenohypophysial tissue in vitro were measured in rats after treatment with betamethasone. The content of CRH and ACTH in the hypothalamus and pituitary gland respectively were markedly reduced. After stopping the treatment the hormone concentrations in both structures returned to normal with the rise in the hypothalamus preceding that in the pituitary gland. Adenohypophysial tissue from betamethasone-treated rats incubated with hypothalamic extracts from control animals showed a considerable reduction in its ability to synthesize and release ACTH. However, corticotrophin release was impaired in adenohypophyses removed from untreated rats and incubated with betamethasone but synthesis was not affected. The physiological significance and the possible clinical relevance of the results are discussed.
INTERACTION OF MORPHINE AND HYPOGLYCAEMIA IN STIMULATING THE RELEASE OF GROWTH HORMONE IN THE RAT
Authors: BLUET-PAJOT M. T. , SCHAUB C.
Published: December 2008

Unité de Neuroendocrinologie, INSERM – U.159, 2ter rue d'Alésia, 75014 Paris, France

(Received 16 February 1977)

It has been reported by Kokka, Garcia, George & Elliott (1972) and Martin, Audet & Saunders (1975) that morphine stimulates the release of growth hormone (GH) in the rat. Previous studies from this laboratory indicated that another narcoanalgesic, gamma-hydroxybutyrate (GHB), is able to stimulate immunoreactive GH secretion, but the pattern of this response differs markedly from that elicited by morphine (M. T. Bluet-Pajot & C. Schaub, unpublished results). We have also used GHB and eliminated stress effects to demonstrate that GH secretion in the rat can be induced by controlled hypoglycaemia as in primates (Bluet-Pajot, Schaub & Nassiet, 1976).

In the present study we have investigated whether morphine could elicit a GH response under GHB narcoanalgesia, and whether GH secretion induced by spontaneous or provoked hypoglycaemia interfered with this effect.

Automated blood glucose monitoring
EFFECT OF VARIOUS BLOOD SAMPLING TECHNIQUES ON SERUM LEVELS OF PITUITARY AND THYROID HORMONES IN THE RAT
Authors: DÖHLER K.-D. , VON ZUR MÜHLEN A. , GÄRTNER K. , DÖHLER U.
Published: December 2008

Section of Clinical Endocrinology, Department of Medicine, and Zentrales Tierlabor, Medizinische Hochschule Hannover, 3000 Hannover 61, Germany

(Received 23 March 1977)

The laboratory rat has served many researchers as an excellent model in the study of endocrine mechanisms. However, the great disadvantage of this animal, especially for the endocrinologist, is its sensitivity toward many types of stress (Ducommun, Sakiz & Guillemin, 1966; Neill, 1970; Ajika, Kalra, Fawcett, Krulich & McCann, 1972; Harms, Langlier & McCann 1975). It has been shown that mild stimuli such as handling or cage transport may have significant effects on the release of pituitary, adrenal and thyroid hormones in the male rat (Baldwin, Colombo & Sawyer, 1974; Euker, Meites & Riegle, 1975; Döhler, Gärtner, von zur Mühlen & Döhler, 1977). To obtain accurate information about the genuine state of endogenous hormone circulation, it is of great importance to select blood sampling procedures which have little or
ROLE OF THE PARATHYROID GLANDS IN THE ENHANCEMENT OF INTESTINAL CALCIUM ABSORPTION IN RESPONSE TO A LOW CALCIUM DIET
Authors: FOX J. , SWAMINATHAN R. , MURRAY T. M. , CARE A. D.
Published: December 2008

The phenomenon of adaptation of intestinal calcium absorption to changes in dietary calcium has been studied in conscious pigs with Thiry–Vella jejunal loops. The result of decreasing the calcium content of the diet from 1·2 to 0·1% was an increase in the efficiency of the net absorption of calcium from the fluid used to perfuse the jejunal loop; this increase took place 4–6 days after the change in diet. A similar effect was noted in four pigs which had previously been parathyroidectomized and in two thyroparathyroidectomized pigs with thyroxine replacement therapy. The effect seen in the parathyroidectomized animals was not attributable to an increase in the concentration gradient of calcium ions between the jejunal lumen and the blood after the change to the low calcium diet. There was a marked increase in the amount of calcium-binding protein in the mucosa taken from the distal three-quarters of the small intestine of intact pigs fed a low calcium diet. However, after parathyroidectomy, the level of calcium in the diet had no significant effect on the amount of calcium-binding protein in the small intestine.

It is concluded that, in pigs, neither parathyroid hormone nor calcitonin is necessary for intestinal adaptation to a low calcium diet and that, although this adaptation may be mediated by 1,25-dihydroxycholecalciferol, a significant increase in the level of calcium-binding protein in the intestine is only seen when the parathyroid glands are intact.
PREVENTION OF CENTRAL DEFEMINIZATION BUT NOT MASCULINIZATION IN MALE RATS BY INHIBITION NEONATALLY OF OESTROGEN BIOSYNTHESIS
Authors: VREEBURG J. T. M. , VAN DER VAART PAULA D. M. , VAN DER SCHOOT P.
Published: December 2008

An inhibitor of aromatization, androsta-1,4,6-triene-3,17-dione (ATD), was administered to newborn male and female rats and various parameters of gonadal and sexual function were examined in adulthood. Males injected with 1 mg ATD on the day of birth (day 1) and on days 3, 5, 10 and 15 postnatally, subsequently (day 55) showed normal male and female copulatory behaviour, but were not able to maintain cyclicity in ovarian transplants. When the ATD was administered by Silastic implants, however, cyclicity in ovarian transplants did occur. Neither form of treatment brought about significant changes in neonatal plasma or testicular testosterone concentrations.

Female rats implanted on day 3 of life with Silastic capsules containing ATD and then given an injection of 0·25 mg testosterone propionate on day 5 subsequently showed normal ovarian function, whereas the controls receiving only testosterone propionate showed persistent vaginal cornification, anovulation and polyfollicular ovaries.

The results support the view that the central conversion of testicular androgens to oestrogens during the neonatal period is necessary to abolish cyclic gonadotrophin release and to suppress female copulatory behaviour.
EFFECTS OF OESTRADIOL AND PROGESTERONE ON THE INDUCTION AND DURATION OF SEXUAL RECEPTIVITY IN CYCLIC FEMALE RATS
Authors: SÖDERSTEN P. , HANSEN S.
Published: December 2008

Intact 4-day cyclic rats showed sexual receptivity 24 h after an injection of oestradiol benzoate (OB) on any day of the cycle except on the second day after the display of spontaneous oestrus. Ovariectomy at the time of OB treatment abolished the behavioural response, but receptivity was restored by progesterone. Progesterone treatment early on the day of behavioural oestrus advanced the display of receptivity but did not affect the time at which oestrus ended. Repeated treatment of sexually receptive rats with progesterone did not affect the duration of oestrus. These results show that sexual receptivity in the intact rat cannot occur in the absence of oestradiol and progesterone. The results further suggest that progesterone may not be associated with the mechanisms terminating behavioural oestrus in rats. Treatment with OB on the day of oestrus can prolong the duration of receptivity but only at a higher dosage than that needed for induction of receptivity.
STEROID AND PROSTAGLANDIN CONCENTRATIONS IN THE PLASMA OF PREGNANT EWES DURING INFUSION OF ADRENOCORTICOTROPHIN OR DEXAMETHASONE TO INTACT OR HYPOPHYSECTOMIZED FOETUSES
Authors: KENDALL J. Z. , CHALLIS J. R. G. , HART I. C. , JONES C. T. , MITCHELL M. D. , RITCHIE J. W. K. , ROBINSON J. S. , THORBURN G. D.
Published: December 2008

Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 μg/h) or dexamethasone (1 mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals, while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2α increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production or parturition.
FAILURE OF DIHYDROTESTOSTERONE TO ELICIT SEXUAL BEHAVIOUR IN THE FEMALE CAT
Authors: CERNY VERONICA A.
Published: December 2008

Laboratory of Anatomy, Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, U.S.A.

(Received 28 March 1977)

Testosterones have stimulatory effects on peripheral target tissue and sexual behaviour in male and female rats (Beach, 1942), guinea-pigs (Young, 1961; Diamond & Young, 1963), rabbits (Palka & Sawyer, 1966; Beyer & Rivaud, 1973) and cats (Green, Clemente & de Groot, 1957; Young, 1961; Whalen & Hardy, 1970). 5α-Androstan-17β-ol-3-one (dihydrotestosterone, DHT) has stimulatory effects on peripheral target organs, and like testosterones, a negative feedback effect on the pituitary gland and hypothalamus (Feder, 1971).

No behavioural effects were seen in male or female rats when DHT was injected systemically (Beyer, Morali & Cruz, 1971; Feder, 1971) nor in the male rat when it was administered intracerebrally (Johnston & Davidson, 1972). Many experiments support the hypothesis that only androgens that can be aromatized to oestrogens can elicit sexual behaviour and
PITUITARY-ADRENAL RESPONSE TO ETHER STRESS IN THE NEONATAL RAT
Authors: TANG F. , PHILLIPS J. G.
Published: December 2008

Wolfson Laboratory for Research in Gerontology, Department of Zoology, University of Hull, Hull, HU6 7RX

(Received 20 June 1977)

A relative lack of adrenocortical responsiveness to stress has been described in the rat during the period from day 2 to about day 16 of neonatal life (Schapiro, Geller & Eiduson, 1962; Levine, Glick & Nakane, 1967; Corte & Yasumura, 1975) and the reports to date seem to implicate a lack of response of the pituitary gland as the primary cause (Zarrow, Philpott & Denenberg, 1968; Donovan, 1970; Corte & Yasumura, 1975). Since very little work has been done on the response of the pituitary gland to stress in the neonatal rat, the present study was undertaken.

Female Sprague–Dawley rats weighing 300 g were housed at 22 °C with a light : darkness cycle of 12 : 12 h. Mated female rats were isolated on day 1 of pregnancy, and after
EFFECT OF OESTRADIOL INFUSION ON PLASMA GONADOTROPHINS AND OVARIAN ACTIVITY IN PROGESTERONE-PRIMED AND UNPRIMED ANOESTROUS EWES
Authors: PANT H. C.
Published: December 2008

Plasma gonadotrophin and ovarian responses to physiological infusions of oestradiol were examined in anoestrous ewes with and without progesterone priming. Intravenous infusion of oestradiol (1 μg/h) for 24 h followed at 96 h by a second infusion for 12 h (low dose) resulted in simultaneous increases in LH and FSH of magnitude and duration similar to those of ewes at natural oestrus. Infusions of 3 μg/h for 16 h, and again at 96 h for 4 h (high dose) resulted in similar gonadotrophin peaks. Endoscopy revealed that only two out of eight ewes had ovulated despite increased ovarian activity and surges of plasma gonadotrophins.

Other anoestrous ewes were primed with 25 mg progesterone daily for 12·5 days before similar infusions of oestradiol on day 15. In the presence of very low plasma progesterone concentrations (< 1·0 ng/ml) at the onset of infusion, there was no pituitary response to the infusion of a low dose of oestradiol but the gonadotrophins were released after the second high-dose infusion.

Progesterone inhibited the positive feedback on both gonadotrophins but not the negative feedback on FSH. Ovulation occurred in all four ewes which had been progesterone-primed and infused with a high dose of oestradiol.
A MONOHYDROXYLATED METABOLITE OF TAMOXIFEN WITH POTENT ANTIOESTROGENIC ACTIVITY
Authors: JORDAN V. C. , COLLINS MARGARET M. , ROWSBY LINDA , PRESTWICH G.
Published: December 2008

The oestrogenic and antioestrogenic properties of tamoxifen and its monohydroxylated (monohydroxytamoxifen) and dihydroxylated (dihydroxytamoxifen) metabolites have been investigated in the immature rat. Whether administered orally or subcutaneously, monohydroxytamoxifen was more active than tamoxifen as an antioestrogen. Dihydroxytamoxifen was less active than tamoxifen as an antioestrogen, but this derivative alone was unable to induce a uterotrophic response. Both metabolites of tamoxifen were potent inhibitors of the binding of [3H]oestradiol to oestrogen receptors in vitro. It is possible that the metabolites play a supportive role in the antioestrogenic activity of tamoxifen. The potent activity of monohydroxytamoxifen in vivo and in vitro suggests that this compound could be an important new tool for the subcellular investigation of oestrogenic and antioestrogenic events.
PITUITARY-ADRENAL RESPONSE IN MALE RATS SUBJECTED TO CONTINUOUS ETHER STRESS AND THE EFFECT OF DEXAMETHASONE TREATMENT
Authors: TANG F. , PHILLIPS J. G.
Published: December 2008

Wolfson Laboratory for Research in Gerontology, Department of Zoology, University of Hull, Hull, HU6 7RX

(Received 5 April 1911)

Jones, Brush & Neame (1972) reported that the level of adrenocorticotrophin (ACTH) in the plasma returned to the control value as early as 10 min after sham adrenalectomy. In contrast, Cook, Kendall, Greer & Kramer (1973) observed no decline in the level of radioimmunoreactive ACTH in the plasma until 40 min after the onset of a 2·5 min ether stress. Furthermore, the stress levels of ACTH were maintained for 2 h in animals subjected to continual ether stress. Therefore, the levels of both ACTH and corticosterone in sequential samples of plasma from control and dexamethasone-treated rats were measured, in order to see whether a negative feedback mechanism, that acts on the pituitary gland as the level of corticosterone increases, operates even in the presence of continuous stress.

Blood samples were taken
INHIBITION OF NEUROHYPOPHYSIAL HORMONE RELEASE FROM THE ISOLATED RAT NEURAL LOBE BY FERROUS CHLORIDE IN THE INCUBATION MEDIUM
Authors: DYBALL R. E. J. , WRIGHT R. J.
Published: December 2008

A. R. C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT

(Received 12 April 1977)

Both electrical stimulation with steel microelectrodes and injection of iron salts into the preoptic area lead to an increased concentration of luteinizing hormone (LH) in the plasma and ovulation (Everett & Radford, 1961; Dyer & Burnet, 1976).

Initially, iron salts were thought to excite nerve cells but Fe2+ and Fe3+ ions, like most cations, when applied to nerve cells by micro-iontophoresis, inhibit firing (Dyer & Burnet, 1976). Dyer & Burnet (1976) proposed a number of alternative explanations for the electrochemical stimulation of ovulation. They suggested that ferrous or ferric ions might kill or damage some neurones and the resulting cell disruption might lead in turn to the liberation of a sufficient quantity of luteinizing hormone releasing hormone (LH-RH) into the hypophysial portal vessels to cause a surge of LH. Alternatively, ovulation might be stimulated by
GROWTH AND URINE OSMOLARITY IN YOUNG BRATTLEBORO RATS
Authors: DLOUHÁ H. , KŘEČEK J. , ZICHA J.
Published: December 2008

Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia, 142 20

(Received 18 April 1977)

If Brattleboro rats, homozygous (DI) and heterozygous (non-DI) for diabetes insipidus are deprived of water, no difference in urinary osmotic pressure can be detected between the two genotypes before 14 days of age Dlouhá, Křeček & Zicha, 1976). This may arise from a shortage of vasopressin in non-DI rats until week 3 after birth, as has been demonstrated in rats of the Wistar strain (Křeček, Dlouhá & Křečková, 1961). We have attempted to detect differences in osmoregulation in DI and non-DI rats before diabetes insipidus is manifest.

Samples of urine were obtained from 147 young Brattleboro rats by perineal stimulation. In 10- and 14-day-old animals, all procedures were done at 30 °C. Dehydration was induced in 10-, 14-, 18- and 22-day-old rats by water deprivation for 6 h; water diuresis was induced in 14-, 19-
OESTROGEN-INDUCED PROTEIN IN RAT MAMMARY TUMOUR AND UTERUS
Authors: MAIRESSE N. , HEUSON J. C. , GALAND P. , LECLERCQ G.
Published: December 2008

Biology Unit, Institute of Interdisciplinary Research, Free University of Brussels, 115 B Waterloo, 1000-Brussels, Belgium and *Service de Médecine et Laboratoire d'Investigation Clinique, Institut J. Bordet, 1000-Brussels, Belgium

(Received 19 April 1977)

We wish to report evidence for the early induction by oestradiol-17β of a protein in mammary tumours induced in Sprague–Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA). The protein appears to be analogous to the oestrogen-induced protein first discovered in the rat uterus by Notides & Gorski (1966) and widely known as 'induced protein' (IP). Induction of IP by oestradiol-17β has been demonstrated in rodents in several tissues of the female genital tract that are targets for oestrogens (Katzman, Larson & Podratz, 1971; Katzenellenbogen & Leake, 1974; Dupont-Mairesse & Galand, 1975) and correlated with the rate of nuclear accumulation of oestrogen receptors (Katzenellenbogen & Gorski, 1972; Katzenellenbogen, 1975). Therefore, the search for induction of IP in DMBA-induced mammary tumours containing oestrogen
INTERACTION OF THYROID-STIMULATING ANTIBODIES WITH THE HUMAN THYROTROPHIN RECEPTOR
Authors: SMITH B. REES , PYLE GWYNETH A. , PETERSEN V. B. , HALL R.
Published: December 2008

Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb–Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.
ADRENAL AND GONADAL GLUCOSE-6-PHOSPHATE DEHYDROGENASE ACTIVITY IN AGEING RATS
Authors: LEATHEM J. H. , APPEL N. M.
Published: December 2008

Bureau of Biological Research, Rutgers University, New Brunswick, New Jersey 08903, U.S.A.

(Received 24 March 1977)

Dehydrogenase enzyme activity linked to NADP has been implicated in the regulation of steroidogenesis in the adrenal gland and ovary (McKerns, 1964, 1965). Furthermore, glucose6-phosphate dehydrogenase (G6PD) activity increases after trophic hormone stimulation, suggesting a metabolic role in the stimulated cells (Castracane & Leathern, 1976). However, little consideration has been given to G6PD as a metabolic marker in steroidogenic organs in relation to ageing. Trout (1974) found G6PD activity to be greater in the adrenal glands of female than of male Wistar rats, but observed no change with age up to 19 months, whereas Stewart & Hunter (1969) recorded a decline in both adrenal and ovarian G6PD activity in 24-month-old Long-Evans rats. A re-examination of G6PD activity in the adrenal glands, testes and ovaries (which exhibit a decline in the formation of follicles: Leathem
EFFECTS OF PIMOZIDE AND BROMOCRIPTINE ON THE PROLIFERATION OF RAT PITUITARY PARS INTERMEDIA CELLS
Authors: RYCHTER J. , STEPIEŃ H.
Published: December 2008

Department of Experimental Endocrinology, Institute of Endocrinology, Medical Academy of Łódź, Dr. Sterling str. 3, 91-425 Łódź, Poland

(Received 31 May 1977)

The secretory function of the intermediate lobe of the pituitary gland is under hypothalamic control (Howe, 1973; Hadley & Bagnara, 1975). Penny, Thody, Tilders & Smelik (1977) have suggested that the synthesis and release of melanocyte-stimulating hormone (MSH) is mediated by dopaminergic neurones which make synaptic contact with secretory cells in the pars intermedia (Björklund, Moore, Nobin & Stenevi, 1973). We have attempted to examine whether the dopaminergic mechanism is also involved in the control of the mitotic activity of the pars intermedia cells and have studied the effects of pimozide, a dopamine receptor blocker (Anden, Butcher, Corrodi, Fuxe & Ungerstedt, 1970) and 2-bromo-α-ergocriptine (bromo-criptine), a dopamine receptor agonist (Loew, Vigouret & Jaton, 1976) on the mitotic activity of the pars intermedia of the rat pituitary gland.

Twenty-three
EFFECT OF ACTIVE IMMUNIZATION OF THE CYCLIC EWE AGAINST OESTRADIOL-17β
Authors: RAWLINGS N. C. , KENNEDY S. W. , HENRICKS D. M.
Published: December 2008

Six mature cyclic ewes were immunized against an oestradiol-17 β-6-oxo-carboxy-oxime-bovine serum albumin conjugate (oestradiol–protein conjugate). Injection of the conjugate began on day 2 of an oestrous cycle, and subsequent booster injections were given on days 12, 22, 32, 62 and 102.

Six control ewes treated with carrier emulsion alone continued to display regular oestrous cycles, whereas the six immunized ewes failed to return to oestrus after the initiation of treatment. The six immunized ewes failed to ovulate by day 22 of the oestrous cycle in which treatment began, and the preovulatory surge of LH did not occur, although the basal concentration of LH in the jugular plasma rose. The luteal phase of the oestrous cycle in which the first injection of the conjugate was made was normal and three out of six immunized ewes showed typical changes in the cervical mucus at the time of the next expected oestrus. The capacity of the plasma to bind oestradiol-17β rose above the control level after the first booster injection and continued to increase until the end of the experiment, 118 days after the initial treatment. The only significant cross-reactions of the antisera were with oestrone.

The concentration of LH in the plasma rose in parallel with the antisera titres and towards the end of the experiment, a definite episodic pattern of LH secretion was indicated. In immunized ewes the concentration of oestradiol-17β in the plasma increased, reaching 286 ± 36 (s.e.m.) pg/ml, a level far in excess of that found in the normal cyclic ewe. The concentration of progesterone in the circulation was raised for a variable period of time in all immunized ewes between days 30 and 118 after the initial treatment.
LUTEINIZING HORMONE RESPONSIVENESS TO LUTEINIZING HORMONE RELEASING HORMONE IN THE ADULT GUINEA-PIG: DIRECT OVARIAN INVOLVEMENT
Authors: TER HAAR M. B.
Published: December 2008

The effects of intravenous injection of synthetic luteinizing hormone releasing hormone (LH-RH) on the release of LH and FSH have been studied in the adult guinea-pig. In all the experiments the secretion of FSH was apparently unaffected by administration of LH-RH. The release of LH was log dose-dependent over the range 0·5–50 μg LH-RH.

During the female cycle, the maximum increment in the concentration of LH after a single i.v. injection of 0·5 μg LH-RH decreased progressively from day 1 to day 13. Double or triple injections of 1 μg LH-RH at 1 h intervals produced no potentiation on day 3 but progressively greater LH responses occurred on days 7, 10 or 13 of the oestrous cycle. Ovariectomy immediately before the first injection of LH-RH on day 7 blocked the potentiated response to subsequent injections, whereas ovariectomy immediately before the second injection still permitted this potentiation. These results suggest that there is direct ovarian involvement in the potentiated response to LH-RH observed during the later part of the guinea-pig oestrous cycle.

Infusion of LH-RH (1 μg over 200 min) produced a potentiated release of LH in female guinea-pigs on day 7 (but not on day 3) of the oestrous cycle after a delay of 1·5 h. It is proposed that there are two 'pools' of LH in the pituitary gland of the female guinea-pig and that the second pool is 'activated' consequent upon previous hypophysial stimulation of secretion from an ovary containing adequately developed follicles.
PROSTAGLANDIN PRODUCTION BY INTRA-UTERINE TISSUES FROM PERIPARTURIENT SHEEP: USE OF A SUPERFUSION TECHNIQUE
Authors: MITCHELL M. D. , FLINT A. P. F.
Published: December 2008

A technique for the continuous superfusion of small tissue samples in vitro has been applied to the study of prostaglandin production by ovine intra-uterine tissues. Basal and oxytocin-stimulated production of prostaglandins was studied at 120–125 days of pregnancy and after dexamethasone-induced delivery. In general, the relative rate of prostaglandin production by tissues was: foetal cotyledon = maternal cotyledon>myometrium and in quantitative order the prostaglandins produced were prostaglandin E (PGE) > prostaglandin F (PGF) = 13,14-dihydro-15-oxo-prostaglandin F (PGFM). Considerable variation was found between the rates of prostaglandin production in individual sheep. Oxytocin had no effect on the production of prostaglandins by tissues obtained before labour but myometrium and maternal cotyledon obtained at delivery exhibited a significant increase in production of PGE and PGF (though not PGFM) in response to oxytocin. Administration of arachidonic acid increased the production of PGE and PGF by the foetal cotyledon.
CHANGES IN VOLUME, TOTAL PROTEIN AND OVARIAN STEROID CONCENTRATIONS OF PERITONEAL FLUID THROUGHOUT THE HUMAN MENSTRUAL CYCLE
Authors: MAATHUIS J. B. , VAN LOOK P. F. A. , MICHIE E. A.
Published: December 2008

Peritoneal fluid was aspirated during laparoscopy from normal women at various stages of the menstrual cycle. The volume of the fluid was found to be influenced by the stage of the cycle, rising from an early proliferative mean value of 0·8 ml to a mean volume of 18·7 ml after ovulation and decreasing again to a mean volume of 5·4 ml in the late secretory phase. The mean volume of peritoneal fluid obtained from women using the contraceptive pill was 0·8 ml, whereas only negligible amounts of fluid were aspirated at laparotomy from the peritoneal cavity of men.

Despite marked changes in volume, the total protein content of the peritoneal fluid (± 60% of the concentration measured in plasma) remained fairly constant throughout the cycle, although a slightly, but significantly, lower value was found in the late proliferative phase. After ovulation the concentration of oestradiol and progesterone in the peritoneal fluid was higher than in plasma in the majority of cases, suggesting that some follicular fluid had drained into the peritoneal cavity at that time. Progesterone, in contrast to oestradiol, was also found in higher concentrations in peritoneal fluid than in plasma before ovulation.

These results suggest that the volume and ovarian steroid concentration of peritoneal fluid are influenced by cyclic ovarian activity. At least two mechanisms may account for these observations: changes possibly effected by oestradiol in vascular permeability leading to a change of inflow and outflow equilibrium at the level of the peritoneal membranes and ovarian–peritoneal transfer of fluid after and possibly also before follicular rupture.
INCREASES IN STEROID BINDING GLOBULINS INDUCED BY TAMOXIFEN IN PATIENTS WITH CARCINOMA OF THE BREAST
Authors: SAKAI F. , CHEIX F. , CLAVEL M. , COLON J. , MAYER M. , POMMATAU E. , SAEZ S.
Published: December 2008

The effects of tamoxifen on cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) were studied in 25 women and one man with breast cancer. These patients were in various endocrine states according to age (15 post-menopausal women) or previous endocrine surgery (ovariectomy, two patients; ovariectomy plus adrenal surgery, five patients; hypophysectomy, three patients; ovariectomy plus hypophysectomy, two patients). The administration of tamoxifen (20–40 mg/day) resulted in increases in the level of CBG in all patients (mean rise in binding capacity 10·8 μg cortisol/100 ml plasma) and in the level of SHBG in 21 patients (mean rise in binding capacity 0·79 μg dihydrotestosterone/ 100 ml plasma for all patients). These increases were positively correlated. They were not associated with any alteration in the association constants of the steroid binding globulins. The effect of tamoxifen on CBG diminished with increasing age. The changes in the levels of CBG and SHBG were independent of the endocrinological state of the patient. It is inferred that tamoxifen has a direct oestrogen-like action on the liver which results in increased production of CBG and SHBG. Tamoxifen therapy for carcinoma of the breast appeared to be least effective in those patients in whom the drug caused the highest increase in the concentration of CBG.
RADIOIMMUNOASSAY OF OXYTOCIN
Authors: DAWOOD M. Y. , RAGHAVAN K. S. , POCIASK C.
Published: December 2008

The evaluation of a radioimmunoassay of oxytocin is described. The method involved careful collection and transportation of blood at 4 °C, acidification of the plasma, extraction with Fuller's earth and radioimmunoassay using antisera raised in rabbits immunized against oxytocin conjugated to bovine serum albumin and 125I-labelled oxytocin. The antisera showed insignificant cross-reaction with a variety of small peptides including vasopressin and vasotocin. The limit of detection of the assay was 2·5 pg with intra-assay and interassay coefficients of variation of 7–15% and 12–18% respectively. Seventy-seven per cent (88 out of 116) of the pregnant women tested had detectable maternal plasma oxytocin. Serial samples of maternal plasma showed a significant increase in oxytocin from the first to the second stage of labour and a significant decrease in the third stage. Oxytocin concentrations in the umbilical arterial plasma were significantly higher in patients in labour. The significance of these findings is discussed.
EFFECTS OF GONADECTOMY AND OESTRADIOL TREATMENT ON PLASMA LUTEINIZING HORMONE CONCENTRATIONS IN THE MARMOSET MONKEY, CALLITHRIX JACCHUS
Authors: HODGES J. K.
Published: December 2008

A heterologous double-antibody radioimmunoassay for marmoset LH is described in detail. The system uses NIAMDD rat LH-I-1 for iodination, NIAMDD rat LH-RP-1 as standard and anti-ovine rabbit LH 610V serum. The assay measures the level of marmoset LH in plasma and shows a maximum cross-reaction (B/Bo = 50%) of < 0·3% with other rat, human or bovine pituitary hormones.

The heterologous assay has been applied to the measurement of the level of LH in the marmoset after gonadectomy and after the subsequent implantation of oestradiol-17β capsules. A clear increase in the concentration of LH in the plasma was observed by day 3 after gonadectomy and in most animals the level reached a plateau by day 9. The rates of increase in the concentration of LH and the maximum levels attained after gonadectomy were similar in male and female marmosets. The secretion of LH in long-term gonadectomized marmosets was episodic. In four of the marmosets studied, the frequency of the pulsatile discharges of LH was circhoral, whereas in the remaining five animals the frequency could not be determined.

Subcutaneous implants containing oestradiol-17β were seen to have a biphasic effect on the secretion of LH in all gonadectomized marmosets. After a transient increase in the concentration of LH (positive feedback) on day 1, levels fell markedly by day 4 and were undetectable 8 days after the implants were introduced (negative feedback).
EFFECT OF INTRAVENOUS INFUSION OF A STEROID ANAESTHETIC ON THE PREOVULATORY SURGE OF LUTEINIZING HORMONE AND OVULATION IN INTACT RATS
Authors: RABII J. , CLIFTON D. K. , SAWYER C. H.
Published: December 2008

Department of Anatomy and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90024, U.S.A.

(Received 21 July 1977)

The existence of a 'critical period' in the ovulatory surge of pituitary gonadotrophin during the afternoon of pro-oestrus was demonstrated by Everett, Sawyer & Markee (1949). It was assumed that during this period, between 14.00 and 16.00 h, an amount of gonadotrophin sufficient to cause ovulation was released from the anterior pituitary gland. Administration of a number of neuropharmacologically active drugs before or during the 'critical period' was shown to inhibit the ovulatory response (Everett, 1961). Recently, Blake (1974) described the existence of an 'activation period' as well as a 'potential activation period' for the preovulatory release of luteinizing hormone (LH) in female rats. The 'activation period' is an extended 'critical period', from 14.00 to 17.00 h, during which time a neurohumoral signal continues to stimulate the anterior pituitary gland
EFFECT OF NON-STEROIDAL ANTI-OESTROGENS ON THE CONCENTRATION OF RAT UTERINE PROGESTERONE RECEPTORS
Authors: JORDAN V. C. , PRESTWICH G.
Published: December 2008

Department of Pharmacology, School of Medicine, Leeds, LS2 9NL

(Received 10 August 1977)

Oestradiol produces hyperplasia of the rat uterine endometrium whereas anti-oestrogens produce hypertrophy (Kang, Anderson & DeSombre, 1975). At the subcellular level, oestradiol stimulates an increase in the concentration of progesterone receptors (Milgrom & Baulieu, 1970) and we have now compared the response to oestradiol with that to two non-steroidal anti-oestrogens, tamoxifen (trans-1-(4-β-dimethylaminoethoxyphenyl)-1, 2-diphenyl-but-1-ene) and monohydroxytamoxifen (1-(4-β-dimethylaminoethoxyphenyl)-1-(4-hydroxyphenyl)-2-phenyl-but-1-ene; Jordan, Collins, Rowsby & Prestwich, 1977).

Mature female rats (130–150 g, Alderley Park strain) were ovariectomized under ether anaesthesia and used for experiments 4 days later. Oestradiol-17β (5 μg), tamoxifen (50 μg) and monohydroxytamoxifen (50 μg) were injected s.c. in 0·1 ml arachis oil and the animals were killed after 6, 24, 48 or 72 h. Controls received arachis oil alone. Uteri were dissected out and weighed wet on a torsion balance. Tissues were homogenized (4 °C) in 2 ml Tris
EFFECT OF HYPOTHYROIDISM ON THE HEPARIN-STIMULATED RELEASE OF LIPASE FROM THE ISOLATED PERFUSED RAT LIVER
Authors: JUBELIN J. , LAM VAN G. , BOYER J.
Published: December 2008

Service d'Explorations Métaboliques, Hôpital de la Conception, 13385 Marseille Cedex 4, France

(Received 24 August 1977)

Indirect observations, derived from the assay of lipase in the blood from human subjects after administration of heparin, have suggested that diseases of the thyroid gland are associated with alterations in the activity of lipolytic enzymes (Porte, O'Hara & Williams, 1966; Kirkeby, 1968; Nikkilä & Kekki, 1972; Tulloch, Lewis & Russel-Fraser, 1973; Jubelin, Bettendorf & Boyer, 1974; Krause, Levy & Fredrikson, 1974). Lipoprotein lipase activity has been measured in adipose tissue from hypothyroid subjects and was found to be normal or raised in rats (Shafrir & Biale, 1971) and reduced in men (Pykälistö, Goldberg & Brunzell, 1976). This work was undertaken to assess alterations in the activity of hepatic lipase during hypothyroidism.

Male Wistar rats (200–220 g) were thyroidectomized and injected (i.p.) 15 days later with 100 μ 131I. A period of 1 month
DIRECT EFFECT OF HISTAMINE ON CORTISOL AND CORTICOSTERONE PRODUCTION BY ISOLATED DOG ADRENAL CELLS
Authors: HIROSE T. , MATSUMOTO I. , AIKAWA T.
Published: December 2008

Department of Physiology, Nagasaki University School of Medicine, Nagasaki, Japan

(Received 2 September 1977)

In the dog, intravenous injection of histamine produces a marked increase in adrenocortical secretion (Suzuki, Hirai, Yoshio, Kurouji & Yamashita, 1963; Papp, Stark, Ács & Varga, 1964; Asano, 1966; Katsuki, Ito, Watanabe, lino, Yuji & Kondo, 1967; Tanigawa, 1967; Narita, 1971; Yamashita, Shimizu, Mieno & Kawao, 1973; Hirose, Matsumoto & Suzuki, 1976; Hirose, Matsumoto, Aikawa & Suzuki, 1977). The adrenocortical response of the dog to histamine was found to be markedly reduced, although not completely eliminated, by hypophysectomy (Hirose et al. 1976, 1977). This indicates that the response, although dependent for the main part on the pituitary gland, may involve a direct effect of histamine on the adrenal cortex or some other extrapituitary factor. In the present study, a direct stimulatory effect of histamine on the adrenal cortex was examined by evaluating the production of cortisol
EFFECT OF OESTRADIOL ON THE INDUCTION OF PEROXIDASE IN VARIOUS TISSUES OF THE IMMATURE RAT
Authors: JELLINCK P. H. , NEWCOMBE ANNE-MARIE
Published: December 2008

Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada

(Received 14 September 1977)

It has been shown previously (Lyttle & Jellinck, 1972) that an enzyme that catalyses the binding of oestradiol-17β to protein in the presence of H2O2 is absent from the uteri of immature rats, but can be induced by physiological doses of oestradiol-17β or gonadotrophin. The induction of peroxidase in the rat uterus under various endocrine conditions has also been investigated (Jellinck & Newcombe, 1977a) and good correlation has been obtained between the ability of compounds to induce the enzyme and their oestrogenic activity (Jellinck & Newcombe, 1977b). In this paper we report on the activity of peroxidase in tissues other than the uterus and the effect of ovariectomy, hypophysectomy and treatment with oestradiol-17β on the levels of this enzyme.

Peroxidase was prepared from tissues of immature (26–29 days old) Holtzman rats weighing 70–90 g as described
PREGNANT MARE SERUM GONADOTROPHIN AND FOLLICLE-STIMULATING HORMONE STIMULATION OF CYCLIC AMP PRODUCTION IN RAT SEMINIFEROUS TUBULE CELLS
Authors: FARMER SUSAN WALKER , PAPKOFF HAROLD
Published: December 2008

Pregnant mare serum gonadotrophin (PMSG) was found to stimulate the production of cyclic AMP in isolated rat seminiferous tubule cells. The PMSG was equipotent with highly purified ovine FSH. The subunits of PMSG were inactive in this system but recombination resulted in partial restoration of activity, and the combination of PMSG α-subunit with FSH β-subunit was even more active. Desialation of PMSG, but not of ovine FSH, resulted in a reduction of slope and potency of this response, suggesting that sialic acid may be important for the interaction of PMSG and the Sertoli cell. Further tests of the responsiveness of this cell preparation demonstrated activity with several species of mammalian FSH molecules, but not with FSH molecules obtained from non-mammalian species.
INTRAPANCREATIC REGULATION OF HORMONE SECRETION IN THE DOMESTIC FOWL, GALLUS DOMESTICUS
Authors: HAZELWOOD R. L. , LANGSLOW D. R.
Published: December 2008

The intrapancreatic endocrine regulation of hormone secretion by the chicken pancreas was studied. Fasted adult male chickens were prepared surgically for the collection of 'gastric' juice and blood samples from the femoral artery. Avian hormone preparations of insulin, glucagon and pancreatic polypeptide (APP) were injected at doses of 50 μg hormone/ kg body wt. Immunoassays of insulin, glucagon and APP were carried out on plasma, as were analyses for glucose, uric acid and free fatty acids (FFA). Gastric juice was analysed for volume flow and total protein, free acid and pepsin concentrations.

Injection of insulin decreased all gastric parameters markedly (in contrast to its effect in mammals) and also increased the concentrations of FFA, glucagon (a bimodal response) and uric acid. The increases in levels of FFA, glucagon and uric acid occurred as early as 2·5 min after injection and considerably before significant hypoglycaemia was induced (15–30 min). Injection of glucagon caused a modest decrease in the volume of gastric secretion, but had little other effect except for a small increase in the amount of pepsin released. At 2·5 min, glucagon gave rise to a significant increase in the levels of insulin and FFA in the plasma, and after 15 min the levels of glucose and uric acid had also increased. A progressive decrease in the concentration of APP in the plasma was observed, which was greatest after 15 min and was 28% below control values. In all respects, APP was a powerful avian gastric secretogogue, but had no effect on the concentrations of plasma glucose and insulin. Whereas APP decreased the concentration of FFA in the plasma immediately, the peptide increased both the total and pancreatic levels of immunoreactive glucagon by 50% within 2·5 min, and this increase was even greater at 15 min.

Collectively, the results obtained indicate, on a temporal basis, that intrapancreatic regulation of endocrine secretion occurs in Aves and that the release phenomena produce an immediate response. Subsequent or secondary hormone release may occur in response to peripheral metabolic events, especially those requiring homeostatic corrective measures.