Effect of ethanol on follicle stimulating hormone-induced steroidogenic acute regulatory protein (StAR) in cultured rat granulosa cells.

Steroidogenic acute regulatory protein (StAR) plays a critical role in trophic hormone-stimulated steroid biosynthesis by facilitating the transfer of cholesterol across the mitochondrial membrane, where the cytochrome P450scc enzyme resides to initiate steroid hormone biosynthesis. Because follicle stimulating hormone (FSH) is a critically important regulator of estradiol (E2) synthesis in granulosa cells and because ethanol is known to suppress gonadotropin-stimulated ovarian steroidogenesis, we evaluated the effects of ethanol on FSH-stimulated StAR in ovarian granulosa cells. Granulosa cells from immature rats pretreated with pregnant mare serum gonadotropin were cultured for 24 h in serum-free medium, either alone (medium only) or with FSH (25 ng/ml) in the presence or absence of ethanol (50 mM).

Effects of chronic systemic administration of opioid peptides, naloxone and N-acetyl beta-endorphin antiserum on gonadotropins and testicular functions in the rat.

Systemic administration of opioid peptides, methionine-enkephalin and beta-endorphin, chronically, lowered gonadotropin levels in plasma and had an inhibitory effect mainly on the testicular enzymes hyaluronidase, acid phosphatase and on incorporation of 3[H] thymidine in the tissue. When rats were similarly treated with opioid peptide antagonist naloxone and N-acetyl beta-endorphin antiserum, induced an opposite effect. This is either the direct effect of opioid peptides/antagonist on the gonads or it may be via the circulating levels of gonadotropin.

Studies on the effect of intratesticular administration of opioid peptides, naloxone or N-acetyl beta-endorphin antiserum on some testicular parameters in rats.

Opioid peptides have been localized in a variety of peripheral tissues like placenta, thyroid, pancreas, gastrointestinal tract, in the reproductive tract of male and female and in the testes of rats. Immunoassayable material was detected in extracts of gonads, reproductive tract and accessory reproductive organs. Studies with naloxone have suggested that beta-endorphin may have an important role in steroidogenesis and may have a role in regulating transport of luminal material.

Testicular lactate dehydrogenase and sorbitol dehydrogenase activity after intratesticular injection of dynorphin and morphine in male rats.

Testicular lactate dehydrogenase (LDH) and sorbitol dehydrogenase (SDH) activity were measured at 1 and 4 hr following intratesticular injection of morphine and dynorphin. Twenty five and 50 micrograms doses of morphine sulfate significantly reduced LDH activity at 1 hr after injection. Five and 25 micrograms doses of dynorphin reduced LDH activity both at 1 and 4 hr after treatment.

Physiological significance of neurotensin in pituitary glycoprotein hormone release as revealed by in vivo and in vitro studies with neurotensin antiserum.

The neuropeptide, neurotensin, is localized to neurons within the hypothalamus which project to the median eminence. It is released from the terminals in the median eminence into the hypophyseal portal vessels and is carried to the gland. The content in the pituitary gland cells may be partly related to the delivery of the peptide via the portal vessels, but it also appears to be produced directly in pituitary cells.

Prolactin suppression during pre and post-implantation periods on rat uterine glucosamine synthase activity.

Administration of bromocriptine (Bc), an ergot derivative having dopamine receptor agonist activity, to rats on day 1-5 of pregnancy prevented implantation of blastocysts and significantly suppressed uterine glucosamine 6-phosphate synthase activity. There was no effect on implantation or the enzyme activity when Bc was injected on day 7 or later of pregnancy. Injection of prolactin following Bc partially restored the enzyme activity and increased number of implantation sites.

Anti-implantation role for substance P and neurotensin in rat.

Substance P (SP) and neurotensin (NT), two structurally related peptides with contrasting biological actions, have been shown to have some role in peripheral reproductive processes. Intrauterine microinjection of SP or NT on day 4 or 5 of pregnancy in the rat significantly reduced the number of viable fetuses, weight and glycogen content of the uterus. The number of viable fetuses, uterine weight or glycogen content were not modified when SP/NT was microinjected on day 8, 9, 10 or on day 14, 15 and 16.

Acute and short-term effects of intraventricular injection of somatostatin and LHRH on glutamate and GABA levels in rat brain.

Glutamate and GABA content in different regions of adult female rat brain were determined at 10 and 30 min following intraventricular injection of LHRH or somatostatin. Cerebral cortex, cerebellar and hypothalamic glutamate levels were significantly elevated at 30 min following injection of 1 micrograms somatostatin, whereas hypothalamic glutamate levels were elevated at 10 min following a 0.5 micrograms dose.

Control of anterior pituitary hormone secretion by neurotensin.

Neurotensin is localized in discrete populations of neuronal cell bodies with terminals in the hypothalamus and median eminence. High-affinity binding sites for neurotensin have been demonstrated not only in the hypothalamus but also in the pituitary gland. These studies suggest a role for neurotensin in control of hypothalamic-pituitary function.

Glutathione and gamma-glutamyl transpeptidase in the adult female rat brain after intraventricular injection of LHRH and somatostatin.

Glutathione content and glutamyl transpeptidase activity in different regions of adult female rat brain were determined at 10 and 30 min following intraventricular injection of LHRH and somatostatin. Hypothalamic glutathione levels were significantly elevated at 10 and 30 min after a single injection of a 0.1 micrograms dose of LHRH.

Glutathione distribution in rat brain at different ages and the effect of intraventricular glutathione on gonadotropin levels in ovariectomized steroid-primed rats.

Glutathione levels were estimated in different regions of the brain of 21-, 30-, 40-, 42-, 45-day-old and adult female rats. Glutathione content in the cerebral cortex, cerebellum and the brain stem remained almost the same beginning from day 21 to sexually mature adult rats. There is a significant increase in hypothalamic glutathione content reaching a peak at puberty (42 days) and thereafter decreasing to the adult levels.

Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release.

Previous studies have indicated that the brain peptide neurotensin can stimulate prolactin release by direct action on the pituitary gland, whereas its action within the hypothalamus is inhibitory. The inhibitory action is mediated by the release of dopamine into the hypophyseal portal veins, which deliver the neurotransmitter to the anterior pituitary gland to inhibit prolactin release. Our experiments were done to evaluate the physiologic significance of these neurotensin actions by injecting the globulin fraction of highly specific neurotensin antiserum either intravenously or intraventricularly.

A new non-hormonal antifertility drug DL-204: II. Effect on testicular hyaluronidase and gamma-glutamyl transpeptidase in male rats.

Effects of DL-204, 2-(3-ethoxyphenyl)-5,6-dihydro (5,1-a)-isoquinoline, a non-hormonal antifertility drug on testicular hyaluronidase and gamma-glutamyl transpeptidase levels, biochemical markers for testicular function, were evaluated in male rats. Treatment of 21-day-old rats with DL-204 for 7 or 15 days produced cryptorchid condition. Testicular hyaluronidase and gamma-glutamyl transpeptidase levels reveal that DL-204 acts on the testes, possibly in two ways; one, by reducing the gonadotropin levels thereby reducing the levels of androgens as reflected by reduced accessory reproductive organ weights and, secondly, by a direct action on the testes.

A new non-hormonal antifertility drug DL-204: I. Effects on testes and accessory glands of reproduction in male rats.

The effect of DL-204, 2-(3-ethoxyphenyl)-5,6-dihydro-5-triazole (5,1a)-isoquinoline, a non-hormonal post-implantational anti-fertility drug, on tissue weights, nucleic acids and total protein concentrations in the testes, ventral prostate and seminal vesicles were evaluated in immature and sexually mature rats, while changes in DNA synthesis were studied only in the immature rats. Treatment of 21-day-old rats at doses of 5mg and 10mg/kg bw once daily for 15 days had no effect on body weight but reduced the weights of testes and accessory glands of reproduction. The concentration of DNA increased while RNA and protein decreased significantly.

The effects of the cholecystokinin antagonist, proglumide, on prolactin secretion in the rat.

Since cholecystokinin produced important effects on prolactin secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of prolactin release. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after injection of the compound.

Differential responses of hypothalamic cAMP and cGMP to substance P and neurotensin in ovariectomized rats.

Hypothalamic cAMP and cGMP levels in ovariectomized rats were evaluated after intravenous (IV) pulse injection and/or intraventricular (IVT) injection of substance P and/or neurotensin. Intravenous substance P lowered hypothalamic cAMP concentration whereas IVT injection of 2.5 micrograms substance P produced significant increase in cAMP levels.

The effects of the cholecystokinin antagonist, proglumide, on gonadotropin release in the rat.

Since cholecystokinin had manifest effects on anterior pituitary hormone secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of gonadotropin secretion. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after the injection of the compound.

A new non-hormonal antifertility drug DL 111-IT: II. Effects on testicular hyaluronidase activity in male rats.

Effects of DL-111, [3-(2-ethylphenyl)-5-(3-methoxyphenyl-1H-1,2,4-triazole] a non-hormonal antifertility agent, on testicular hyaluronidase activity, an accurate biochemical marker for testicular function, were evaluated in male rats. Treatment of 21-day-old rats with DL-111 sc for 7 or 15 days resulted in a significant fall in testicular weight and complete suppression of hyaluronidase activity. During the 30-day post-treatment the enzyme activity was restored to normal levels.

A new non-hormonal antifertility drug DL 111-IT: I. Effects on testes and accessory glands of reproduction in male rats.

Effect of DL-111, 3-(2-ethylphenyl)-5-(3-methoxyphenyl-1H-1,2,4-triazole, a non-hormonal postimplantational antifertility agent, on testicular and accessory reproductive organ weights and total protein, RNA and DNA concentrations were evaluated in immature and adult rats. Treatment of 21-day-old rats at doses of 2.5 mg and 5 mg/kg body weight decreased body weight, weights of testes and accessory glands of reproduction.

Recent developments in female contraception: LHRH.

During the last few years new approaches to female contraception based on LHRH and its analogs have been developed. The physiological significance of pulsatile LHRH release and its stimulation of the pituitary has been elucidated by recent studies in rhesus monkey. Immunization against LHRH results in complete inhibition of reproductive function in animals and may find as a useful method of long-term fertility control in domestic animals.

Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus.

Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of 3H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis.

Hypothalamic tyrosine hydroxylase activity, plasma gonadotropin and prolactin levels after aminooxyacetic acid in ovariectomized rats.

Plasma concentrations of gonadotropin, prolactin and hypothalamic tyrosine hydroxylase (TH) activity were measured in ovariectomized rats treated with aminooxyacetic acid (AOAA), a drug which elevates brain GABA levels. Hypothalamic TH activity was significantly increased with a significant decrease in prolactin (Prl) release. Plasma levels of gonadotropins were not modified by AOAA.

Involvement of catecholamines and glutamate in GABAergic mechanism regulatory to luteinizing hormone and prolactin secretion.

There is some evidence that a population of estrogen-receptive neurons exists in the preoptic/anterior hypothalamic area which uses gamma-aminobutyric acid (GABA) as neurotransmitter and which is involved in mediating the negative feedback of estrogens on pituitary luteinizing hormone (LH) secretion. These neurons are proposed to be presynaptic inhibitors to norepinephrine (NE) release thereby inhibiting the stimulatory effect of NE on LHRH neurons. Muscimol, a potent GABA agonist, inhibits pituitary LH release in ovariectomized rats after intraventricular injection of 5 nmol.

Hypothalamic tyrosine hydroxylase activity and plasma gonadotropin and prolactin levels in ovariectomized-steroid treated rats.

Plasma gonadotropin, prolactin levels and hypothalamic tyrosine hydroxylase (TH) activity were evaluated in ovariectomized (OVX) estradiol benzoate (EB) or progesterone (P) treated rats. Single injection of 10 micrograms or daily injection of 5 micrograms EB/rat for 7 days significantly lowered gonadotropin levels in OVX animals and elevated PRL levels. Single injection of 2 mg or daily injection of 200 micrograms P/rat for 7 days increased gonadotropin and PRL levels.