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M Ferin

Publications and source records attributed to M Ferin.

At least 73 records · Page 4Linked to original sources
PubMed1984

Endogenous opioid peptides and the control of the menstrual cycle.

This paper reviews recent experimental evidence which supports a role for endogenous opioid peptides in the control of gonadotropin function. In primates, cell bodies containing endogenous opioid peptides have been located within the hypothalamus in areas rich in gonadotropin-releasing hormone (GnRH) and dopamine. The release of beta-endorphin from these hypothalamic neurons is influenced by gonadal steroids, maximal release being observed when both estradiol and progesterone are present. beta-Endorphin has been shown to decrease LH secretion, and naloxone, an opiate antagonist, reverses this action. The LH-releasing activity of naloxone parallels variations in hypothalamic beta-endorphin secretory activity, so that maximal effects are seen during the luteal phase of the cycle. Present evidence indicates that opiates exert their effect on LH via a hypothalamic site. It is concluded that increased opioid inhibition of the GnRH-LH axis is responsible for the decline in LH pulse frequency during the luteal phase. The studies provide evidence for a chemical basis rationalizing relationships between reproductive function and stress, and have further implication on other forms of amenorrhea.

Amenorrhea↗
PubMed1984

Reduced frequency of pulsatile luteinizing hormone secretion in the luteal phase of the rhesus monkey. Involvement of endogenous opiates.

Pulsatile secretion of LH in women has been shown to vary during the menstrual cycle. LH pulse frequency during the luteal phase is markedly reduced compared to that in the follicular phase. The objectives of the present study were to determine if similar changes in pulsatile LH secretion occur in the monkey, and whether endogenous opiates are involved in producing these changes. In order to document if LH pulse frequency is reduced in the nonhuman primate luteal phase, serial blood samples were collected from 10 rhesus monkeys at 15-min intervals for 6 h at 3 different times of the luteal phase (early, mid-, and late). This pattern of secretion was contrasted to that observed during the ensuing early follicular phase. LH pulse frequency during the luteal phase was significantly reduced compared to the early follicular phase. Mean pulse frequency (+/- SE) was 0.84 +/- 0.16 pulses/6 h in the luteal phase vs. 2.99 +/- 0.58 pulses/6 h in the early follicular phase. When endogenous opioid activity was blocked during the luteal phase by a 5-h continuous infusion of naloxone (2 mg/h), an opiate antagonist, LH pulse frequency was increased to 2.48 +/- 0.25 pulses/5 h. This frequency was markedly different from the frequency of 0.85 +/- 0.17 pulses/5 h observed in the control period which immediately preceeded the naloxone infusion. The mean amplitude of the LH pulses in the luteal phase, which was significantly greater than that observed in the early follicular phase (20.9 +/- 1.9 ng/ml and 11.7 +/- 0.3 ng/ml) was not affected by naloxone (23.5 +/- 2.4 ng/ml vs. 25.3 +/- 1.9 ng/ml). Infusion of naloxone for longer periods (9 h) in 3 additional monkeys caused an increase in LH pulse frequency which was maintained in 2 of the monkeys, whereas the third animal exhibited only an acute response (a single pulse). These results indicate that the reduction in LH pulse frequency that occurs in the luteal phase of the rhesus menstrual cycle is an event in which endogenous opiates participate. Our previous finding that beta-endorphin release from neurons in the median eminence is stimulated during the luteal phase of the monkey, together with the present results, suggest that beta-endorphin functions as a modulator of pulsatile LH secretion in the primate menstrual cycle.

Animals↗
PubMed1984

Adrenocorticotropin immunoactivity in monkey hypophyseal portal blood.

ACTH was measured with both C-terminal and midportion antibodies in monkey hypophyseal portal plasma, and compared to levels in monkey peripheral plasma, medial basal hypothalamus, and anterior pituitary. In nine female monkeys, mean hypophyseal portal blood C-terminal ACTH immunoactivity was 5290 +/- 2010 (SEM) pg/ml, whereas the mean midportion ACTH level was 949 +/- 178 pg/ml. These immunoactivities were not lower in two monkeys that were completely hypophysectomized 30 min before portal blood collection. The ratio of C-terminal to midportion ACTH immunoactivity was 4:1 in two monkey medial basal hypothalami, and 1:1 in four monkey anterior pituitary glands. Gel filtration of hypophyseal portal plasma extract and of medial basal hypothalamus showed that the C-terminal ACTH immunoactivity eluted in the same position as the corticotropin-like-intermediate lobe peptide standard. The similarity of the C-terminal to midportion ACTH ratios in monkey medial basal hypothalamus and portal blood, and the observation that ACTH immunoactivity was not significantly lower in two hypophysectomized monkeys suggests that portal blood C-terminal ACTH immunoactivity is of hypothalamic rather than pituitary origin. We conclude that monkey hypophyseal portal blood contains high levels of a C-terminal fragment of ACTH, which coelutes with corticotropin-like intermediate lobe peptide on gel filtration, and which is secreted from the brain directly into the portal circulation.

Adrenocorticotropic Hormone↗
PubMed1983

The effect of hypophysectomy and gonadotropin administration on the distribution and quantity of LH-RH in the brains of platyfish: a combined immunocytochemistry and radioimmunoassay study.

Radioimmunoassay (RIA) and immunocytochemistry (ICC) were used to study the effect of hypophysectomy (H) on the distribution and quantity of luteinizing hormone-releasing hormone (LH-RH) in the brains of sham-operated-saline-injected, H-saline-injected and H-gonadotropin (GTH)-injected mature female platyfish (Xiphophorus maculatus). In fish hypophysectomized for 5 weeks, there was a decrease in the LH-RH content of the brain (mean +/- S.E. = 446 +/- 31 pg, H-saline-injected; 649 +/- 28 pg, sham-operated-saline-injected). The administration of five 10-micrograms injections of salmon GTH on alternate days beginning in the fifth week of H resulted in a small but significant (P less than 0.05) decrease in LH-RH beyond H-saline-injected group levels (362 +/- 36 pg). The ICC analysis of H fish indicated a decrease in immunoreactive (ir)-LH-RH in the nucleus preopticus periventricularis (NPP) and nucleus lateralis tuberis pars posterioris (NLT), but a marked increase in the immunoreactivity of the neurons in the nucleus olfactoretinalis (NOR). The H fish which received GTH showed a decrease in ir-LH-RH in the NOR, but a slight increase in the NPP and NLT. The results demonstrate that although there is a general decrease in the LH-RH content of brains in H fish as determined by RIA and ICC, one of 3 ir-LH-RH-containing centers of the brain, the NOR, shows a marked increase in ICC-demonstrable LH-RH, indicating that these 3 regions may differ in their roles in the regulation of the reproductive system. The drop in RIA-measurable LH-RH in the brain, along with the enlarged perikarya observed in all 3 regions, suggests that an increase in the synthesis and release of LH-RH occurs in response to removal of the pituitary. The functional significance of the NOR and the feedback mechanisms between brain, pituitary and gonads are discussed.

Animals↗
PubMed1983

Brain tissue grafts in the central nervous system: reversal of hypogonadism.

Transplantation of brain tissue from normal donors into the central nervous system of animals with specific central neurochemical deficiencies has been used to remedy such defects. The present studies demonstrate that the hypogonadism present in the adult male hypogonadal (hpg) mouse that is secondary to hypothalamic gonadotropin releasing hormone (GnRH) deficiency can be corrected by grafts into the anterior third ventricle of fetal preoptic area (p.o.a.) tissue. The p.o.a. is a primary site of localization of GnRH neurones in rodents. As compared with untreated hpg males, or with hpg males that had received control cortical tissue implants, the hpg animals with p.o.a. grafts showed measurable levels of GnRH within the hypothalamus. Immunocytochemical studies revealed GnRH within the transplants. Increased pituitary and plasma LH and FSH, and testicular growth with full spermatogenesis, were also evident in the hpg males that had received p.o.a. implants.

Animals↗
PubMed1983

Naloxone stimulation of luteinizing hormone secretion in the female monkey: influence of endocrine and experimental conditions.

It is known that opiate administration results in the inhibition of LH release. In this paper, we examine the role of endogenous opiates in the regulation of gonadotropin secretion during the menstrual cycle of the monkey. The objectives of these experiments were to determine the experimental and endocrine conditions that are conducive to increased gonadotropin secretion in response to endogenous opiate antagonism. In Exp 1, naloxone was administered during the luteal phase to three groups of monkeys under three different experimental conditions. When naloxone (2 mg, iv) was injected into conscious unrestrained or sedated animals, LH secretion increased 2- to 3-fold. In contrast, the same dose of naloxone failed to stimulate LH secretion in monkeys restrained in primate chairs. In Exp 2, the gonadotropin response to acute naloxone administration on each day of the menstrual cycle was determined. A significant increase in the serum LH concentration (greater than or equal to 20% within 40 min of injection) was observed after naloxone administration in 60% of the trials conducted during the luteal phase. Significant increases occurred in only 13% of the saline-treated control trials during this stage of the menstrual cycle. Mean LH levels increased from 14.4 +/- 1.3 to 31.2 +/- 4.3 ng/ml after naloxone injection. In contrast, naloxone had no effect on LH secretion during the follicular phase. Although small LH increments were noted after naloxone injection in 40 +/- 8% of the trials, neither the frequency nor the amplitude of these increases was different from that in follicular phase controls. We conclude from these results that the ability of naloxone to stimulate LH secretion is limited to the luteal phase. Previous findings from our laboratory indicate that hypothalamic beta-endorphin activity, as reflected by its concentration in hypophyseal portal blood, is increased by ovarian steroids and that its greatest activity occurs during the luteal phase. Since the response of LH to naloxone administration was limited to the luteal phase, we believe that these results support the conclusion that hypothalamic beta-endorphin is a physiological modulator of LH secretion in the monkey.

Animals↗
PubMed1983

Neuroendocrine control of ovarian function in the primate.

This article reviews the neuroendocrine factors which control the menstrual cycle in the macaque monkey. It describes the pulsatile characteristics of gonadotrophin secretion, the control of LH pulses by an arcuate neural Gn-RH oscillator and the significance of pulsatile Gn-RH secretion. The factors which may modulate the activity of the Gn-RH arcuate neural oscillator are anaesthesia, ovarian hormones and endogenous opiates, as well as the possible significance of changes in Gn-RH pulsatile characteristics. Finally, the oestrogen and progesterone feedback control of the mid-cycle gonadotrophin surge and the site of action (hypothalamic or hypophysial) of these steroids are contrasted in the monkey and rat.

Animals↗
PubMed1982

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Amygdala↗
PubMed1982

Brain grafts reverse hypogonadism of gonadotropin releasing hormone deficiency.

Hypogonadism in the mutant hpg mouse is characterized by a deficiency of hypothalamic gonadotropin releasing hormone (GnRH). Affected male mice exhibit immature reproductive organs, small abdominal testes and low pituitary and plasma gonadotropin concentrations. Recent studies have demonstrated the potential of fetal brain transplants to establish functional connections with host tissues. We therefore sought to use this approach to correct the hpg deficit. Fetal preoptic area (POA) (a site of GnRH production) from unaffected animals of the hpg strain was transplanted into the anterior third ventricle of adult hpg mice. We report that in such implanted animals, killed 2 months post-implantation, the POA grafts contained GnRH neurones, from which GnRH-positive fibres could be traced to capillaries of the median eminence. Hypothalamic GnRH and pituitary and plasma gonadotropin concentrations were increased compared with levels in untreated (hpg) animals. The testes were enlarged and had descended into the scrotum. Evidence of full spermatogenesis and interstitial cell development was present in testicular sections. No such effects were seen with transplants of cortical tissue.

Animals↗
PubMed1982

beta-Endorphin in hypophyseal portal blood: variations throughout the menstrual cycle.

Concentrations of beta-endorphin were measured in the venous effluent of the hypothalamus (hypophyseal portal blood) at various phases of the menstrual cycle and after ovariectomy in rhesus and pigtailed monkeys. In the rhesus, beta-endorphin concentrations were high during the mid- to late follicular phase [737 +/- 256 pg/ml (mean +/- SE)] and the luteal phase (1675 +/- 1108) of the menstrual cycle, but were undetectable (less than 133) at menstruation. Concentrations were also high in pigtailed monkeys during stages of the menstrual cycle other than at menstruation (4870 +/- 1090 pg/ml), but undetectable (less than 133) 4--12 months after ovariectomy. These results indicate that beta-endorphin concentrations in hypophyseal portal blood are related to menstrual cycle events, probably changes in ovarian steroids; this in turn suggests that beta-endorphin may participate in the ovarian feedback regulation of gonadotropin secretion.

Animals↗
PubMed1982

Effects and site of action of morphine on gonadotropin secretion in the female rhesus monkey.

The effects of morphine on gonadotropin secretion, and the site of its action, were tested in female rhesus monkeys. In Exp 1, morphine sulfate (3, 6, or 9 mg iv) was injected into ovariectomized monkeys, and its effects on tonic (pulsatile) LH and FSH secretion were examined. Administration of morphine (9 mg) resulted in a significant decrease in circulating LH and FSH, which lasted for 4-5 h. Exp 2 was performed to evaluate the site of action of morphine, whether hypophyseal or suprahypophyseal. The effects of morphine (6, 9, or 12 mg) on the LH response to GnRH pulses were evaluated in stalk-sectioned monkeys, in which gonadotropin secretion had been restored by long term pulsatile infusion of GnRH. LH responses to GnRH were not significantly altered by morphine. Exp 3 was performed to determine the effects of morphine on the estrogen-induced LH surge. Estradiol benzoate (330 micrograms in oil) was administered on days 2-5 of the menstrual cycle to nine animals. Four of these also were injected with 9 mg morphine at 5-h intervals for 40 h. Four of the five control and three of the four morphine-treated monkeys showed similar LH surges. The results demonstrate that, in the monkey, opiates inhibit tonic (pulsatile) gonadotropin secretion, most probably by acting at a suprahypophyseal site. In contrast, morphine does not alter the estradiol-induced LH surge, a result that differs from that seen in lower species and that may be related to differences in estradiol positive feedback characteristics.

Animals↗
PubMed1982

Effect of sex steroids on beta-endorphin in hypophyseal portal blood.

Previous studies in female monkeys have shown that beta-endorphin (beta-EP) of hypothalamic origin is present in high concentrations in the hypophyseal portal blood and declines at the time of menses and after ovariectomy. In this study we have examined the effects of estradiol and progesterone replacement on portal blood beta-EP in ovariectomized monkeys. After acute iv administration of estradiol (2 micrograms), beta-EP did not rise from previously low levels (less than 133 pg/ml) over the ensuing 3 h. After chronic estradiol replacement for 3 weeks, portal beta-EP was detectable in 2 of 4 ovariectomized monkeys, with peak values of 341 and 733 pg/ml, respectively. When progesterone as well as estradiol were replaced chronically, high levels of beta-EP, [1610 +/- 192 (SE) pg/ml] were measured in all 13 portal blood samples collected from 4 ovariectomized monkeys. The majority of the beta-EP immunoactivity in these samples eluted from a Sephadex G-50 column in the same position as synthetic human beta-EP. Cation exchange chromatography showed that the majority of immunoactive beta-EP in portal plasma appeared to be nonacetylated beta-EP (1-31). We conclude that ovarian steroids are necessary for the release of hypothalamic beta-EP into portal blood and suggest that cyclic changes in sex steroids may affect anterior pituitary function in part via a mechanism involving hypothalamic beta-EP.

Animals↗