Hypothalamo-hypophyseal-gonadal function in the rat following administration of the novel and selective D-1 agonist CY 208-243

Summary The effects of the novel and selective dopamine D-1 agonist CY 208-243 on the rat hypothalamo-hypophyseal-gonadal (HHG) axis were studied. CY 208-243 did not modify the concentration of luteinizing hormone (LH) in serum from female or male rats, and had no effect upon opiate antagonist-induced stimulation of LH secretion in male rats. CY 208-243 did not inhibit ovulation in cycling female rats. Thus, D-1 receptor activation by systemic drug administration does not alter HHG function in rats.     

Influence of light on the plasma gonadotropin concentrations in the newborn rat.

The physiological increase in plasma gonadotropin (LH and FSH) levels in newborn rats is indisputably influenced by light. Permanent illumination accentuates this increase, whereas darkness decreases it in 16-day-old female rats. In male rats of the same age, only permanent illumination was tested with the same results.     

Effects of monosodium glutamate on circulating concentrations of luteinizing hormone and growth hormone in young growing domestic fowl (Gallus domesticus)

Summary The administration of monosodium glutamate (MSG) at a dose of 4 g/kg in 5-day-old fowl or 5 daily injections of MSG (total dose 20 g/kg) in 1- to 5-day-old fowl did not affect body growth in either male or female domestic fowl. Neither MSG treatment schedule affected either testis weight or the circulating concentration of luteinizing hormone (LH). A small, but significant decrease in the plasma concentration of growth hormone (GH) was observed in female chicks which had received daily MSG injections.Acknowledgments. Paper of Journal Series, New Jersey State Experiment Station, project No. 18141 and 18443, supported by State and Hatch Act funds and grants from the National Science Foundation (PCM 80227227) and the Upjohn Company.     

Influence of light on the plasma gonadotropin concentrations in the newborn rat

Summary The physiological increase in plasma gonadotropin (LH and FSH) levels in newborn rats is indisputably influenced by light. Permanent illumination accentuates this increase, whereas darkness decreases it in 16-day-old female rats. In male rats of the same age, only permanent illumination was tested with the same results.Acknowledgments. We would like to thank Dr C. Kordon (Unité de Neurobiologie, INSERM, rue d'Alésia, F-75014 Paris) who welcomed us in his laboratory and advised us on these experiments.     

Activité gonadotrope d'un extrait d'urines de femmes en ménopause

Summary In agreement with earlier observations on hypophysectomized male rats, a purified extract from pooled menopausal urine has been shown to contain follicle-stimulating (FSH) as well as luteinizing (LH) activity. Its administration to immature hypophysectomized female rats increased ovarian and uterine weights and induced follicle growth and the formation of corpora lutea. If the activity of the extract is measured in standardized units by bioassay in intact female mice using the uterine weight, the dose needed for corpus luteum formation in the hypophysectomized female rat seems to be approximately ten times higher than the dose producing interstitial cell repair and complete spermatogenesis in the hypophysectomized male.

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2^e Communication: Effets sur les ovaires de rates impubères hypophysectomisées.     

Luteinizing hormone content of the pars tuberalis of the hypophysis of neonatally androgenized female rats

Summary The immunoreactive LH content of the pars tuberalis of neonatally androgenized female rats was studied and found to be significantly lower than that of control females at oestrus or of control males. It is concluded that the rat pars tuberalis does secrete LH and that this secretory activity is diminished by neonatal androgenization in a manner that differs from that reported for the LH secretion in the pars distalis.This investigation received financial support from Direccion de Investigacion, grants RMS-80-13 and S-80-26, Universidad Austral de Chile.     

Absorption of iron from gut into blood: Sex- and time-related studies in rats

Summary As judged from 2-h blood level curves, adult female rats absorbed more Fe^II per cm² of gross duodenal mucosa than adult male rats. By contrast, the 2-h blood level curves per cm² of mucosa of proximal jejunum did not differ significantly in male and female rats although in both sexes, iron was absorbed more efficiently from the duodenum. This research was supported by grant RO1 AM 12381 from the National Institute of arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health.     

Similarity between the effects of suprachiasmatic nuclei lesions and of pinealectomy on gonadotropin release in ovariectomized,sulpiride-treated and melatonin-replaced rats

The aim of this study was to compare the effects of pineal indole treatments on LH and FSH release in pinealectomized and suprachiasmatic lesioned and ovariectomized rats rendered hyperprolactinemic by acute sulpiride treatment. pinealectomy or suprachiasmatic nuclei lesions in female rats both decreased plasma LH and FHS at 10, but not at 20 d after surgery, whereas the daily afternoon administration of melatonin effectively restored levels of both gonadotropins to control values. In ovariectomized rats, pinealectomy or suprachiasmatic nuclei lesions were ineffective in counteracting the high plasma levels of LH and FSH. However, sulpiride treatment in both pinealectomized and suprachiasmatic nuclei lesioned and castrated female rats significantly decreased the levels of LH and FSH, an effect which was counteracted by daily afternoon melatonin administration. Other pineal indoles tested, i.e., 5-hydroxy- and 5-methoxytryptophol, were ineffective in regulating gonadotropin levels. The results suggest that the pineal gland, through its hormone melatonin, can modulate gonadotropin secretion by acting on a dopamine mechanism independent of hypothalamic suprachiasmatic areas.     

Studies on the modulation of the desensitization of the pituitary gland by luteinizing hormone-releasing hormone in the ovariectomized rat

In ovariectomized rats the desensitization of the LH cells in vivo, which develops during constant rate infusion of LHRH, 1) does not depend on a concomitant depletion of the pituitary LH stores, 2) proceeds normally when the hypothalamo-pituitary connection has been severed and 3) is a process in which LH itself is not involved.     

Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats.

Estradiol in vitro produces a significant increase in the incorporation of 3H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.     

Studies on the modulation of the desensitization of the pituitary gland by luteinizing hormone-releasing hormone in the ovariectomized rat

Summary In ovariectomized rats the desensitization of the LH cells in vivo, which develops during constant rate infusion of LHRH, 1) does not depend on a concomitant depletion of the pituitary LH stores, 2) proceeds normally when the hypothalamo-pituitary connection has been severed and 3) is a process in which LH itself is not involved.     

Effects of prolactin (PRL) on gonadotropin release in mice with congenital PRL deficiency

Summary In prolactin (PRL)-deficient male dwarf mice, treatment with PRL stimulates the release of FSH without affecting plasma LH levels. We now report that this effect of PRL is not mediated by the testes and that PRL does not modify FSH or LH release in female dwarf mice.This work was supported by the National Institute of Child Health and Human Development through a grand HD12642 and RIA Core of grant HD10202. We thank NIAMDD and Drs G.D. Niswender and L.E. Reichert, Jr, for reagents used in radioimmunoassays.     

Effects of injury on the concentration of alpha1-macroglobulin and alpha2-macroglobulin in the plasmas of male and remale rats.

The effects of injury on the concentration of alpha1-macroglobulin and alpha2-macroglobulin in the plasmas of male and remale rats has been investigates. At 5 days after injury to the male rats the alpha1-macroglobulin concentration increased to 131% of its preinjury value. The alpha2-macroglobulin concentration increased more rapidly to a maximum of 86 times its initial value. In the female rats alpha2-macroglobulin increased only slightly and alpha1-macroglobulin not at all.     

Comparison between serum LH and FSH levels in male and female rats during the perinatal period]

In the newborn female Rat, no transient LH and FSH serum surges were observed between 0 and 2 hrs., as compared with the newborn male. In the newborn female, a progressive increase in serum gonadotropins was observed between 2 and 6 hrs. These results indicate that, at birth, the pituitary-gonadal axis reacts in a different way in male and female Rats.     

Effect of estrogens on LH- and FSH-levels in prepuberal male and female androgenized rats

Summary This paper has demonstrated that neonatal androgenization increases in prepuberal male and female rats the FSH-levels without changes in LH, indicating that the sexual differences in the control of FSH is a relevant process that takes place during the differentiation of the hypothalamus.Supported by a grant from the Consejo Nacional de Investigaciones Cientificas y Técnicas, Rep. Argentina.Acknowledgment. We are grateful to NIAMD, Rat Pituitary Program, for the reagents for the radioimmunoassays.     

Calmodulin-associated post-translational regulation of rat organic cation transporter 2 in the kidney is gender dependent

In this work, regulation of organic cation transporter type 2 from rat (rOCT2) stably transfected in HEK293 cells was investigated by microfluorimetry with 4-(4-(dimethylamino)styryl)-N-methylpyridinium as substrate. The transport mediated by rOCT2 was specifically stimulated by PKA, phosphatidylinositol-3-kinase, p56^lck tyrosine kinase, mitogen-extracellular-signal-regulated-kinase-1/2, calmodulin (CaM), and CaM-kinase-II. The regulatory pattern of rOCT2 differs markedly quantitatively and qualitatively from that of other OCT isoforms. Only CaM-dependent upregulation is conserved throughout the OCT family. For this reason, CaM regulation of rOCT2 was also investigated in isolated S3-segments (known to express only rOCT2) of male and female rat proximal tubules. Inhibition of CaM by calmidazolium significantly decreased rOCT2 activity (−49.0 ± 13.6%, n = 4) in male but not female (9.0 ± 13.0%, n = 4) rats. Real-time PCR and Western blot investigations of CaM expression in rat kidneys showed that male animals have significantly higher CaM expression. This is the first study describing post-translational gender-dependent rOCT2 regulation. Received 26 February 2009; accepted 16 March 2009     

Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats

Summary Estradiol in vitro produces a significant increase in the incorporation of³H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.Supported by a grant from the Consejo Nacional de Investigaciones Cientifícas y Técnicas de la República Argentina.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Summary Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.