Reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area in rams

1992 ◽  
Vol 132 (2) ◽  
pp. 201-215 ◽  
Author(s):  
G. A. Lincoln ◽  
K.-I. Maeda
Keyword(s):  
Reproductive Cycle ◽  
Preoptic Area ◽  
Plasma Concentrations ◽  
Mediobasal Hypothalamus ◽  
Reproductive Effects ◽  
Long Day ◽  
Reproductive Axis ◽  
Micro Implants ◽  
The Brain ◽  
Short Days

ABSTRACT The reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus (MBH) and preoptic area (POA) were monitored in Soay rams. Groups of animals were initially conditioned to alternating 16 weekly periods of long days (16 h light:8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal reproductive cycle. All experiments were then initiated at 10 weeks under long days when the animals were sexually inactive. In experiment 1, rams were exposed to short days for 14 weeks or maintained on long days to illustrate the photoperiodically induced re-activation and regression of the reproductive axis. In experiments 2–4, rams received micro-implants of melatonin in the MBH or POA, or received control treatments (sham-operated or no surgery) for 12–14 weeks while maintained on long days (total of 12 animals/treatment). The melatonin implants consisted of 22-gauge stainless-steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain. Incubation of the implants in Tricine-buffered saline (pH 8·0) at 37 °C showed that the release rate of melatonin was relatively constant after an initial peak in week 1 (means ± s.e.m.: 3·42 ± 0·43 μg/24 h). Rams with melatonin implants placed in the MBH, but not in the POA, showed a consistently earlier re-activation of the reproductive axis compared with the control animals in all three experiments (12/12 for MBH vs 2/12 for POA). The mean time to maximum testicular diameter was 12·2 ± 0·9, 21·6 ± 1·8 and 22·3 ± 1·2 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P < 0·01; analysis of variance). The premature growth of the testes in the MBH group was associated with an earlier increase in the blood plasma concentrations of FSH and testosterone, and the appearance of the sexual skin coloration. Removal of the implants resulted in a decline in all reproductive parameters. The melatonin treatments did not cause a detectable increase in the peripheral concentrations of melatonin, or affect the diurnal rhythm in melatonin which reflected the long-day photoperiod. When implants containing 125I-labelled melatonin were introduced into the brain the associated radioactivity was localized to within 1 mm of the implants. The overall results demonstrate that the constant administration of melatonin into the MBH blocks the effect of the endogenous long-day melatonin signal and induces gonadal redevelopment. This provides the first evidence that melatonin acts within or close to the MBH to relay effects of photoperiod and influence the timing of the reproductive cycle in the ram. Journal of Endocrinology (1992) 132, 201–215

Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area on the secretion of prolactin and β-endorphin in rams

1992 ◽  
Vol 134 (3) ◽  
pp. 437-448 ◽  
Author(s):  
G. A. Lincoln ◽  
K.-I. Maeda
Keyword(s):  
Body Weight ◽  
Preoptic Area ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Early Summer ◽  
Mediobasal Hypothalamus ◽  
Continuous Administration ◽  
Blood Concentrations ◽  
Micro Implants ◽  
Short Days

ABSTRACT In a previous study, we showed that the local administration of melatonin into the mediobasal hypothalamus (MBH), but not the preoptic area (POA), caused a premature increase in the secretion of FSH and growth of the testes in sexually inactive Soay rams exposed to long days. To extend these observations, we have now measured blood concentrations of prolactin and β-endorphin and the associated peripheral responses in the same animals, to establish whether the treatments produced multiple endocrine changes such as those which occur following exposure to short days. Groups of rams were initially exposed to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal cycles in the secretion of the pituitary hormones. The treatments were started at 10 weeks under long days, when the animals had a physiology characteristic of the early summer with high blood plasma concentrations of prolactin (associated with growth of the summer pelage), and low concentrations of β-endorphin (associated with low body weight). The animals were assigned at random to the following treatments: (i) micro-implants of melatonin in the MBH, (ii) microimplants of melatonin in the POA, (iii) empty implants in the MBH or POA to act as operated controls, and (iv) no surgery to act as unoperated controls (n=12 rams/treatment). The micro-implants consisted of 22-gauge stainless-steel needles with melatonin fused inside the tip. The implants were inserted bilaterally in the brain, and left in place for 12–14 weeks. The observations continued for a total of 28 weeks while the animals remained under long days. The administration of melatonin in the MBH induced a rapid decrease in plasma concentrations of prolactin while in the POA it induced a less marked but significant effect. The mean times to minimum concentrations of prolactin were 7·4±0·4, 17·3±2·8 and 26·0 ±0·3 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P<0·001, POA vs control P<0·01. In the MBH group, the concentrations of prolactin subsequently increased to a maximum 6 weeks after the end of melatonin treatment. The changes in prolactin were accompanied by changes in growth and moulting of the pelage; only animals in the MBH group showed a conspicuous moult associated with the change from low to high prolactin secretion. There was also a marked effect of melatonin when given into the MBH, but not the POA, on plasma concentrations of β-endorphin, which was correlated with differences between groups in the cycle in body weight. In conclusion, continuous administration of melatonin into the MBH acts like a long-duration melatonin signal and induces a full sequence of biological responses normally evoked by transfer to short days. This is used as evidence that melatonin acts within or close to the MBH to induce the multiple effects of photoperiod in the ram. Journal of Endocrinology (1992) 134, 437–448

scholarly journals Production of inhibin A not B in rams: changes in plasma inhibin A during testis growth, and expression of inhibin/activin subunit mRNA and protein in adult testis

Reproduction ◽  
2002 ◽  
pp. 827-835 ◽  
Author(s):  
AS McNeilly ◽  
CJ Souza ◽  
DT Baird ◽  
IA Swanston ◽  
J McVerry ◽  
...  
Keyword(s):  
Reproductive Cycle ◽  
Negative Feedback ◽  
Plasma Concentrations ◽  
Inhibin B ◽  
Significant Activity ◽  
Inhibin A ◽  
Subunit Mrna ◽  
Long Day ◽  
Lighting Regimen ◽  
Short Days

Previous studies have shown that changes in the plasma concentrations of immunoreactive inhibin measured by radioimmunoassay occur in parallel with growth and regression of the testes during a reproductive cycle in adult Soay rams induced by exposure to an artificial lighting regimen of alternating 16 week periods of long days and short days. With the development of new two-site ELISAs for sheep inhibin A and inhibin B, we have re-examined the relationship between FSH and dimeric, biologically active inhibin in the reproductive cycle in adult Soay rams. No signal was generated by sheep testicular extract, ram or ewe plasma, or sheep ovarian follicular fluid in the inhibin B ELISA. In contrast, ram plasma contained significant activity in the inhibin A ELISA, which diluted in parallel to the inhibin A standard, and was abolished by preincubation of ram plasma with monoclonal antibodies specific for the betaA, but not the betaB, subunit. These results indicate that the ram is the first adult male mammalian species identified to date in which the testes produce and secrete dimeric inhibin A and not inhibin B. Northern blot analysis and immunocytochemistry confirmed the presence of alpha, betaA and betaB inhibin/activin subunit mRNA and protein in the testes of adult rams. Changes in plasma inhibin A concentrations occurred in parallel with the growth and regression of the testes during the long day: short day: long day lighting regimen in adult Soay rams, confirming our previous observations with immunoreactive inhibin. During the growth phase of the testes in the first 8 weeks of exposure to short days there was a positive correlation between plasma FSH and inhibin A concentrations, indicating that during this phase the secretion of inhibin A is stimulated by FSH and that inhibin A did not act as a negative feedback hormone on FSH secretion. From week 8.5 to week 16.0 of exposure to short days, there was a negative correlation between FSH and testosterone concentrations, but not inhibin, indicating that when inhibin concentrations are high, testosterone acts as the negative regulator of FSH secretion. Thus, in intact adult rams, when the testes are fully active it appears that inhibin A may sensitize the pituitary to the negative feedback effects of testosterone, at which time they act synergistically to maintain plasma concentrations of FSH.

The irritable male syndrome

2001 ◽  
Vol 13 (8) ◽  
pp. 567 ◽  
Author(s):  
Gerald A. Lincoln
Keyword(s):  
Preoptic Area ◽  
Mood State ◽  
Negative Mood ◽  
Melatonin Receptors ◽  
Interactive Effects ◽  
Reproductive Axis ◽  
Gonadotrophin Secretion ◽  
Arcuate Nuclei ◽  
Seasonally Breeding ◽  
Short Days

The irritable male syndrome (IMS) is a behavioural state of nervousness, irritability, lethargy and depression that occurs in adult male mammals following withdrawal of testosterone (T). The negative mood state has been described in men following withdrawal of androgens and is a striking feature in male seasonally breeding mammals associated with the end of the mating season. The Soay ram provides an animal model for IMS. Rams exposed to alternating 16-week periods of long and short days inactivate the reproductive axis in response to the switch to long days; the rapid decrease in T secretion provokes the symptoms of IMS. The animals appear agitated and fearful, and the incidence of physical wounding owing to fractious inter-male fighting peaks at this time. Androgen and oestrogen receptors expressed in cells in the preoptic area and ventromedial/arcuate nuclei appear to relay the effects of T on behaviour and gonadotrophin secretion, and melatonin receptors expressed in the premammillary area relay the effects of melatonin/photoperiod. Changes in the activity of hypothalamic opioidergic, dopaminergic and serotonergic neural networks may dictate the interactive effects of T and photoperiod. The working hypothesis is that IMS is a transition state associated with low hypothalamic amine levels triggered, in part, by the withdrawal of opioid peptides.

Testosterone sensitivity of the seminal sacs of tree sparrows (Spizella arborea) in different reproductive states

1986 ◽  
Vol 109 (1) ◽  
pp. 125-131 ◽  
Author(s):  
F. E. Wilson
Keyword(s):  
Reproductive Cycle ◽  
Plasma Concentrations ◽  
Plasma Testosterone ◽  
Reproductive State ◽  
Critical Test ◽  
Testosterone Concentration ◽  
Unit Change ◽  
Dependent Growth ◽  
Dose Dependent ◽  
Short Days

ABSTRACT Testosterone sensitivity of the seminal sacs of castrated tree sparrows from each of three reproductive states was evaluated by measuring the change in seminal-sac mass per unit change in the logarithm of replacement or plasma testosterone. Birds were exposed to exogenous testosterone for 38 days. Replacement doses less than 0·17 μmol or plasma concentrations less than about 0·7 nmol/l did not induce seminal-sac growth in photosensitive castrated birds held on short days, in photosensitive castrated birds transferred from short to long days, or in photorefractory castrated birds retained on long days. Higher replacement doses or plasma concentrations, however, stimulated log dose-dependent growth of the seminal sacs in castrated birds from all three reproductive states. The change in seminal-sac mass per unit change in the logarithm of the dose of replacement testosterone was less (P= 0·0495) in photosensitive castrated birds held on short days than in photosensitive castrated birds transferred to long days. A more critical test of sensitivity (i.e. the change in seminal-sac mass per unit change in the logarithm of mean plasma testosterone concentration) indicated, however, that sensitivity of the seminal sacs to testosterone is independent of reproductive state. That result, when considered in the context of the plasma testosterone profile of intact males during a simulated reproductive cycle, argues that the seminal sacs of sexually quiescent (photosensitive or photorefractory) tree sparrows are small not because of their insensitivity to androgens, but because of a deficiency of circulating androgens. J. Endocr. (1986) 109, 125–131

EFFECT OF GONADECTOMY ON THE CONCENTRATIONS OF CATECHOLAMINES IN DISCRETE AREAS OF THE DIENCEPHALON OF THE DOMESTIC FOWL

1981 ◽  
Vol 89 (3) ◽  
pp. 389-397 ◽  
Author(s):  
P. G. KNIGHT ◽  
R. T. GLADWELL ◽  
F. J. CUNNINGHAM
Keyword(s):  
Domestic Fowl ◽  
Thalamic Nucleus ◽  
Testosterone Propionate ◽  
Plasma Concentrations ◽  
Testosterone Replacement Therapy ◽  
Mediobasal Hypothalamus ◽  
Lh Secretion ◽  
The Brain ◽  
Noradrenaline And Adrenaline ◽  
Catecholaminergic Mechanisms

Concentrations of dopamine, noradrenaline and adrenaline in discrete areas of the diencephalon in male and female domestic fowl were correlated with changes in the plasma concentrations of LH induced by gonadectomy. Gonadectomized birds of both sexes exhibited raised plasma concentrations of LH and in castrated cockerels the daily administration of testosterone propionate was completely effective in preventing the post-castration rise in LH. Although no significant alterations in the brain concentrations of noradrenaline or adrenaline were observed in cockerels, the concentration of dopamine in the paraventricular nucleus (PVM), dorsomedial thalamic nucleus and mediobasal hypothalamus (MBH) were significantly raised in castrated compared with sham-operated birds by 136, 182 and 52% respectively. In each case the increase was partially suppressed by testosterone replacement therapy. In pullets, ovariectomy resulted in significant increases in the concentrations of dopamine (83%) and noradrenaline (78%) in the MBH and noradrenaline (35%) and adrenaline (34%) in the PVM. These findings suggest that in the fowl at least part of the negative feedback effect of gonadal steroids on LH secretion may be mediated by catecholaminergic mechanisms at the level of the hypothalamus.

Inhibin concentrations in the peripheral blood of rams during a cycle in testicular activity induced by changes in photoperiod or treatment with melatonin

1989 ◽  
Vol 120 (1) ◽  
pp. R9-R13 ◽  
Author(s):  
G. A. Lincoln ◽  
A. S. McNeilly
Keyword(s):  
Peripheral Blood ◽  
Plasma Concentrations ◽  
Active Phase ◽  
Light Cycle ◽  
Artificial Lighting ◽  
Reproductive Axis ◽  
First Time ◽  
Lighting Regimen ◽  
Short Days

ABSTRACT Changes in the concentration of inhibin, FSH, LH and testosterone were measured in the peripheral blood of adult Soay rams during a reproductive cycle induced by exposure to an artificial lighting regimen (long days with a 16-week period of short days) or treatment with melatonin (long days with a 12-week period when melatonin was administered daily in mid-light phase to simulate the effect of short days). In both experimental situations, changes in the plasma concentrations of inhibin occurred in parallel with the cycle in the diameter of the testes with a four- to fivefold increase in the inhibin concentrations from the nadir to the peak of the testicular cycle. Increases in the plasma concentrations of FSH, LH and testosterone also occurred in association with the reactivation of the reproductive axis. The weekly changes in the plasma concentrations of inhibin were positively correlated with the changes in plasma FSH values during the developing and regressing stages of the testicular cycle but negatively correlated during the active stage. In a group of castrated rams exposed to the same lighting regimen, the plasma concentrations of inhibin were always below the detection limit of the radioimmunoassay. The testosterone values were also very low in the castrates while the plasma concentrations of FSH and LH were 10-50 fold higher than normal and varied in relation to the light cycle. The results show for the first time that inhibin is secreted into the peripheral blood in the ram exclusively from the testes. The positive correlation between the changes in plasma concentrations of FSH and inhibin during the developing and regressing phases of the testicular cycle indicate that FSH stimulates the secretion of inhibin. The negative correlation between FSH and inhibin in the active phase of the testicular cycle, is consistent with the role of inhibin in the negative-feedback control of FSH secretion. This is only evident because the testes undergoes reactivation of its full function during the change from the regressed to the active state which is especially obvious in the highly seasonal Soay ram.

Regulation of female brain aromatase activity during the reproductive cycle of the dove

1992 ◽  
Vol 134 (3) ◽  
pp. 385-396 ◽  
Author(s):  
R. E. Hutchison ◽  
A. W. Wozniak ◽  
J. B. Hutchison
Keyword(s):  
Reproductive Cycle ◽  
Ovarian Development ◽  
Preoptic Area ◽  
Ovarian Follicles ◽  
Substrate Affinity ◽  
Aromatase Activity ◽  
Oestrogen Treatment ◽  
Female Brain ◽  
Brain Aromatase ◽  
The Brain

ABSTRACT Oestrogen is formed in the female dove brain. The aim of this study was to determine whether (a) the catalytic properties of the brain aromatase are similar to the ovarian enzyme and (b) aromatase activity in the female brain changes during the reproductive cycle and is influenced by steroids and environmental stimuli. The results show that female preoptic aromatase has a higher substrate affinity than the enzyme in ovarian follicles (apparent Km: preoptic area, 7 nmol/l; ovarian follicles, 29 nmol/l), but a lower activity in the preoptic area (Vmax: preoptic area, 290 fmol/mg tissue per h; ovarian follicles, 843 fmol/mg tissue per h). In intact females with developing follicles, oestradiol-17β formation was higher in the posterior hypothalamus than the preoptic area. Females in a later stage of reproductive development (yolked follicles) had a different distribution of oestrogen formation with increased aromatase activity in the preoptic area. Preoptic and posterior hypothalamic aromatase activity of females paired with males for 10 days was positively correlated (r = 0·84, P = 0·0001; r = 0·75, P = 0·001 respectively) with ovarian development. Females with undeveloped ovaries which interacted with males had higher preoptic aromatase activity than visually isolated females with similar ovarian development, suggesting that behavioural stimuli have direct effects on brain aromatase activity which are independent of the ovary. Oestradiol benzoate treatment increased preoptic and posterior hypothalamic aromatase activity in intact and ovariectomized females, and testosterone propionate treatment increased anterior hypothalamic aromatase activity, but did not affect other areas, indicating that the distribution of induced aromatase activity is steroid-specific. Oestrogen treatment in ovariectomized or intact females did not replicate the maximal hypothalamic aromatase activity seen when the ovary contained yolked follicles. We conclude that brain aromatase activity is related directly to ovarian condition during the reproductive cycle of the female dove. As in the male, steroids have a role in the regulation of oestrogen formation in the female hypothalamus; behavioural stimuli are also likely to be involved in the control of the brain enzyme. Journal of Endocrinology (1992) 134, 385–396

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz
Keyword(s):  
Body Weight ◽  
Reproductive System ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Control Groups ◽  
Melatonin Treatment ◽  
Exogenous Melatonin ◽  
Reproductive Axis ◽  
Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

scholarly journals Thyroid Hormone and the Neuroglia: Both Source and Target

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Petra Mohácsik ◽  
Anikó Zeöld ◽  
Antonio C. Bianco ◽  
Balázs Gereben
Keyword(s):  
Thyroid Hormone ◽  
Cell Function ◽  
Hormone Regulation ◽  
Mediobasal Hypothalamus ◽  
Iodothyronine Deiodinase ◽  
Neuronal Gene ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Thyroid hormone plays a crucial role in the development and function of the nervous system. In order to bind to its nuclear receptor and regulate gene transcription thyroxine needs to be activated in the brain. This activation occurs via conversion of thyroxine to T3, which is catalyzed by the type 2 iodothyronine deiodinase (D2) in glial cells, in astrocytes, and tanycytes in the mediobasal hypothalamus. We discuss how thyroid hormone affects glial cell function followed by an overview on the fine-tuned regulation of T3 generation by D2 in different glial subtypes. Recent evidence on the direct paracrine impact of glial D2 on neuronal gene expression underlines the importance of glial-neuronal interaction in thyroid hormone regulation as a major regulatory pathway in the brain in health and disease.

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