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Why Bromocriptine can lower testosterone levels and should not always be used during cycle to surpess prolactin .
- Thread starter chazk
- Start date
R
Ross
Guest
chazk said:
You WANT *SUBNORMAL* Prolactin levels while ON CYCLE. This will DECREASE HPTA SENSITIVITY. The HPTA will be inhibited no MATTER WHAT you use.
After cycle is another issue.
Let's take a closer look at some of these studies!
Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback.
Bartke A,
Matt KS,
Steger RW,
Clayton RN,
Chandrashekar V,
Smith MS.
Department of Physiology, Southern Illinois University, School of Medicine, Carbondale 62901.
During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma gonadotropin levels to negative feedback effects of testosterone, while PRL-secreting ectopic pituitary transplants exert an opposite effect. We have examined some of the suspected mechanisms of PRL modulation of testosterone feedback in male golden hamsters. In immature animals, the amount of cytoplasmic androgen receptors in the anterior pituitary was decreased by mild hyperprolactinemia and increased by treatment with bromocriptine, an inhibitor of PRL release. Bromocriptine increased pituitary androgen binding also in adult hamsters. These findings would imply that PRL modulates the responsiveness to negative steroid feedback at the pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 3324676 [PubMed - indexed for MEDLINE]
Prolactin modulates the gonadotropin response to the negative feedback effect of testosterone in immature male rats.
Chandrashekar V,
Bartke A,
Sellers K.
The effects of hyperprolactinemia (hyperPRL) and hypoprolactinemia (hypoPRL) on pituitary gonadotropin secretion and the feedback sensitivity to testosterone (T) were evaluated in immature male rats. At 34 days of age, rats were divided into three groups: group 1, controls, injected with oil; group 2, treated with bromocriptine mesylate (CB-154; 250 micrograms in oil/rat X day); and group 3, subjected to the transplantation of one pituitary from an adult female rat under the kidney capsule and treated with oil. The treatments were continued for 14 days. On day 8, each of these groups were further divided into three subgroups: intact, castrated, and castrated plus T treated. T treatment consisted of injection of T propionate (TP; 50 micrograms in oil/rat) on alternate days starting immediately after castration. Blood samples were obtained by cardiac puncture throughout the study. Plasma PRL levels were significantly reduced by CB-154 treatment and significantly increased by the pituitary graft (P less than 0.001). In intact immature male rats, hyper- or hypoPRL did not affect plasma LH levels, whereas hyperPRL reduced (P less than 0.01) plasma FSH concentrations. The postcastration increase in circulating LH levels was significantly increased (P less than 0.001) in rats treated with CB-154 24 h after castration. Moreover, the suppressive effects of TP on plasma LH and FSH levels were significantly (P less than 0.05) attenuated in hypoPRL rats. In pituitary-grafted rats, effects of castration and TP replacement on plasma LH levels did not differ from those in control rats. These results demonstrate that subnormal levels of PRL reduce the sensitivity of the hypothalamic-pituitary system to feedback inhibition by T. In contrast to previous findings in the adult rats, acute hyperPRL in immature male rats did not affect the negative feedback action of T on gonadotropin secretion.
PMID: 3100279 [PubMed - indexed for MEDLINE]
1: Biol Reprod. 1987 Feb;36(1):138-47. Links
Effects of hyperprolactinemia on the control of luteinizing hormone and follicle-stimulating hormone secretion in the male rat.
Smith MS,
Bartke A.
Experiments were conducted to determine the effects of acute hyperprolactinemia (hyperPRL) on the control of luteinizing hormone and follicle-stimulating hormone secretion in male rats. Exposure to elevated levels of prolactin from the time of castration (1 mg ovine prolactin 2 X daily) greatly attenuated the post-castration rise in LH observed 3 days after castration. By 7 days after castration, LH concentrations in the prolactin-treated animals approached the levels observed in control animals. HyperPRL had no effect on the postcastration rise in FSH. Pituitary responsiveness to gonadotropin hormone-releasing hormone (GnRH), as assessed by LH responses to an i.v. bolus of 25 ng GnRH, was only minimally effected by hperPRL at 3 and 7 days postcastration. LH responses were similar at all time points after GnRH in control and prolactin-treated animals, except for the peak LH responses, which were significantly smaller in the prolactin-treated animals. The effects of hyperPRL were examined further by exposing hemipituitaries in vitro from male rats to 6-min pulses of GnRH (5 ng/ml) every 30 min for 4 h. HyperPRL had no effect on basal LH release in vitro, on GnRH-stimulated LH release, or on pituitary LH concentrations in hemipituitaries from animals that were intact, 3 days postcastration, or 7 days postcastration. However, net GnRH-stimulated release of FSH was significantly higher by pituitaries from hyperprolactinemic, castrated males. To assess indirectly the effects of hyperPRL on GnRH release, males were subjected to electrical stimulation of the arcuate nucleus/median eminence (ARC/ME) 3 days postcastration. The presence of elevated levels of prolactin not only suppressed basal LH secretion but reduced the LH responses to electrical stimulation by 50% when compared to the LH responses in control castrated males. These results suggest that acute hyperPRL suppresses LH secretion but not FSH secretion. Although pituitary responsiveness is somewhat attenuated in hyperprolactinemic males, as assessed in vivo, it is normal when pituitaries are exposed to adequate amounts of GnRH in vitro. Thus, the effects of hyperPRL on pituitary responsiveness appear to be minimal, especially if the pituitary is exposed to an adequate GnRH stimulus. The suppression of basal LH secretion in vivo most likely reflects inadequate endogenous GnRH secretion. The greatly reduced LH responses after electrical stimulation in hyperprolactinemic males exposed to prolactin suggest further that hyperPRL suppresses GnRH secretion.
PMID: 3105612 [PubMed - indexed for MEDLINE]
1: Endocrinology. 1984 Oct;115(4):1506-10. Links
Does prolactin modify testosterone feedback in the hamster? Pituitary grafts alter the ability of testosterone to suppress luteinizing hormone and follicle-stimulating hormone release in castrated male hamsters.
Bartke A,
Matt KS,
Siler-Khodr TM,
Soares MJ,
Talamantes F,
Goldman BD,
Hogan MP,
Hebert A.
Adult male golden hamsters maintained in a long photoperiod (14 h of light and 10 h of darkness) or in a short photoperiod (5 h of light and 19 h of darkness for 7 weeks) were castrated and either given one anterior pituitary transplant under the kidney capsule or sham-operated. Additional animals were castrated and grafted or sham-grafted at the time of transfer to the short photoperiod. Starting 2 weeks after castration, all animals were injected three times a week with 20 micrograms testosterone propionate (TP). After 3 weeks, the dose of TP was increased to 80 micrograms and, after an additional 2 weeks, to 320 micrograms per injection. Blood samples were collected 2 weeks after castration and 1 day after the last injection of 20, 80, and 320 micrograms TP. Short photoperiod reduced and pituitary grafts increased plasma PRL levels. Plasma testosterone levels were related to the dose of injected TP, but were not influenced by photoperiod or pituitary transplants. Before the onset of TP injections, plasma LH and FSH levels in grafted and sham-grafted hamsters did not differ. In each of the three photoperiod conditions, injections of TP were consistently less effective in suppressing plasma gonadotropin levels in pituitary-grafted animals than in sham-grafted controls. These results indicate that PRL modulates the effects of exogenous testosterone on LH and FSH release in adult castrated male golden hamsters, this effect of PRL is due to reducing the sensitivity of the hypothalamic-pituitary system to feedback inhibition by testosterone, and suppression of pituitary PRL release in short photoperiod may be partially responsible for the concomitant increase in the sensitivity of LH and FSH release to inhibition by testosterone.
PMID: 6434293 [PubMed - indexed for MEDLINE]
1: Adv Exp Med Biol. 1987;219:153-75. Links
Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback.
Bartke A,
Matt KS,
Steger RW,
Clayton RN,
Chandrashekar V,
Smith MS.
Department of Physiology, Southern Illinois University, School of Medicine, Carbondale 62901.
During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma gonadotropin levels to negative feedback effects of testosterone, while PRL-secreting ectopic pituitary transplants exert an opposite effect. We have examined some of the suspected mechanisms of PRL modulation of testosterone feedback in male golden hamsters. In immature animals, the amount of cytoplasmic androgen receptors in the anterior pituitary was decreased by mild hyperprolactinemia and increased by treatment with bromocriptine, an inhibitor of PRL release. Bromocriptine increased pituitary androgen binding also in adult hamsters. These findings would imply that PRL modulates the responsiveness to negative steroid feedback at the pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 3324676 [PubMed - indexed for MEDLINE]
1: Endocrinology. 1983 Jan;112(1):22-8. Links
Increased sensitivity to the negative feedback effects of testosterone induced by hyperprolactinemia in the adult male rat.
McNeilly AS, Sharpe RM, Fraser HM.
High plasma levels of PRL induced by transplants of two donor pituitaries under the kidney capsule of adult male rats resulted in a prolonged suppression of plasma levels of LH and FSH although testosterone levels were maintained within normal limits. Castration of rats with pituitary transplants resulted in a normal though delayed rise in serum levels of both LH and FSH to levels equivalent to those in normal castrated controls. This increase in gonadotropin levels occurred in spite of maintenance of elevated PRL levels. Two experiments were carried out in which testosterone was restored after castration by Silastic testosterone-containing implants of various lengths (Exp 1:60, 30, and 10 mm; Exp 2: 30, 20, 10, 5, and 2 mm). In both experiments 60- and 30-mm testosterone implants prevented the postcastration rise in LH and FSH in both control and hyperprolactinemic rats. However, although the shorter testosterone implants delayed this rise in control rats, levels of LH and FSH increased by 4 days and were not significantly different from castrated rats without testosterone implants by 15 days after castration. In contrast, this rise in gonadotropins was abolished or considerably delayed by the shorter implants in hyperprolactinemic rats, demonstrating an increase in sensitivity of the hypothalamic pituitary axis to the negative feedback effects of testosterone in these animals. These results suggest that 1) to maintain suppression of gonadotropin secretion in hyperprolactinemia high levels of PRL alone are insufficient and gonadal steroids are required, and 2) high levels of PRL appear to sensitize the hypothalamic-pituitary axis to the negative feedback effects of gonadal steroids.
PMID: 6401176 [PubMed - indexed for MEDLINE]
1: J Endocrinol. 1999 Feb;160(2):197-203. Links
The antiprogestin RU486 dissociates LH and FSH secretion in male rats:
evidence for direct action at the pituitary level.
Sanchez-Criado JE, Bellido C, Tebar M, Ruiz A, Gonzalez D.
Department of Physiology, Faculty of Medicine, University of Cordoba, Spain.
Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.
Effects of hyper- and hypoprolactinemia on gonadotropin secretion, rat testicular luteinizing hormone/human chorionic gonadotropin receptors and testosterone production by isolated Leydig cells.
Waeber C, Reymond O, Reymond M, Lemarchand-Beraud T.
The effect of prolactin (Prl) on gonadotropin secretion, testicular luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors, and testosterone (T) production by isolated Leydig cells has been studied in 60-day-old rats treated for 4 days, 4 and 8 weeks with sulpiride (SLP), a dopaminergic antagonist, or for 4 days and 4 weeks with bromocriptine (CB), a dopaminergic agonist. Plasma Prl concentrations were significantly greater in the SLP groups (204 +/- 6 ng/ml) and lower in the CB groups (3.0 +/- 0.2 ng/ml) than those measured in the control groups (54 +/- 6 ng/ml). The plasma concentrations of gonadotropin were not affected by a 4-day treatment with SLP or CB, nor were they after a 4-week treatment with CB. However, the hyperprolactinemia induced by an 8-week treatment with SLP was associated with a reduced secretion of gonadotropin (LH, 16 +/- 4 vs. 35 +/- 6 ng/ml; FSH, 166 +/- 12 vs. 307 +/- 14 ng/ml). In SLP-induced hyperprolactinemia, a 30% increase in the density of the LH/hCG testicular binding sites was observed (178 +/- 12 fmol/mg protein), whereas a 60% decrease was measured in hypoprolactinemia (55 +/- 5 vs. control 133 +/- 5 fmol/mg protein). Plasma T levels were increased in 4-day and 4-week hyperprolactinemic animals (4.3 +/- 0.4 and 3.9 +/- 0.4 ng/ml, respectively), but returned to normal levels in the 8-week group (3.0 +/- 0.5 vs. C: 2.3 +/- 0.2 ng/ml). No T modifications were observed in hypoprolactinemic animals. Two distinct populations of Leydig cells (I and II) were obtained by centrifugation of dispersed testicular cells on a 0-45% continuous Metrizamide gradient. Both possess LH/hCG binding sites. However, the T production from Leydig cells of population II increased in the presence of hCG, whereas that of cell population I which also contain immature germinal cells did not respond. The basal and stimulated T secretions from cell populations I and II obtained from CB-treated animals were similar to controls, whereas from 4 days to 8 weeks of hyperprolactinemia, basal and hCG induced T productions from cell population II decreased progressively. These data show that hyperprolactinemia causes, in a time-dependent manner, a trophic effect on the density of LH/hCG testicular receptors; reduces basal and hCG-stimulated T production from isolated Leydig cells type II; and results in an elevated plasma T concentration which decreases with time. The latter suggests a slower T catabolism and/or an impaired peripheral conversion of T into 5 alpha-dihydrotestosterone (DHT). Although hypoprolactinemia is associated with a marked reduction in testicular LH receptors, it does not affect T production.
PMID: 6299412 [PubMed - indexed for MEDLINE][/QUOTE]
chazk
New member
no you dont are you blind can you not read these human studies?not golden hamsters.castrated hamsters or studies in rats BUT REAL HUMAN STUDIES!- Ross - said:
lowering prolactin decreases the binding of LH to the Leydig cell LH receptor, with a concomittent reduction in androgen production (17).
subnormal amounts of prolactin cuases just the opposite effect it shuts you down harder..
you dont want high prolactine levels....you dont want them to low..
you never anwsered this question proof above shows sumbnormal prolactin levels inhibits lh and the hpta..
why would someone with normal levels on a primo/masteroncut up cycle
want to lower prolactin and get shut down?
when prolacton was never a issue in the first place...
I dont care about your male rat or castrated hamster studies HUMAN studies show subnormal prolactin is very bad for the hpta.
R
Ross
Guest
chazk said:
Normal levels of Prolactin are what keep the HPTA SENSITIZED to androgens. It is required in the negative feedback loop.
REMOVE prolactin while on cycle, and you will DECREASE the HPTA's ability to "sense" the exogenous steroids.
We DO NOT WANT NORMAL LEVELS WHILE ON CYCLE! This is why people experience HPTA SHUTDOWN!
We want SUBNORMAL levels of prolactin, as in people with PITUITARY TUMORS. When these people with pituitary tumors were given TESTOSTERONE the tunmor PREVENTED SHUTDOWN! Because these tumors prevented prolactin secretion.
chazk
New member
we dont have tumors ross were not trying to shut down our pituitary glands,- Ross - said:
prolactin is necessary for androgen uptake .Our pituitary glands also secret LH if we shut it it down we have no LH to stimulate test production.. meaning no prolactin no pituitary LH means no testosterone out put from the human body none what so ever ITS IS TOTALLY SHUT DOWN not only surpressed but totally off.
*****bromocriptine competitively inhibits androgen production at the level of the testicular enzymes 17 alpha-hydroxylase and/or 17,20-lyase. These enzymes act at intermediate steps in the testicular production of testosterone*****
means your testicles do not produce anything and are shut down harder then with just the steroids alone....
high levels of prolactin creates a shut down effect..
normal levels of prolactin cuases the pituitray glad to still put out LH and still make testosterone at a surpressed level but not totally shut off..
take away the prolactin and your further surpressing the pituitary glads production of LH and testicular function..
your theory is just that ross a theory with out human studies you have no proof .
all you have cited is castrated hamsters,golden hamsters and male rats.
Good nite ross I expect lots of googling from you with actual proof to back up your claims..
please list the effects of
*to much prolactin in humans
*subnormal prolactin in human
*normal prolactin in human
with these studies you find.
dont want to read studies your using now they have no merit and are pretty much all fluff rambling about castrated hamsters
chazk
New member
- Ross - said:
no human studies showed that ross.
the tumors prevented prolactin secretion .. thats what cuased then people to not even make testosterone the lack or prolactin and they had to be supplemented with testosterone .
ofcoarse they did not shut down becuase they were not even outputting a enough testosterone to begin with..
low prolactin = now test levels end of story
R
Ross
Guest
chazk said:
You missed the boat.
You obviously have no scientific background WHATSOEVER.
If you aren't intelligent enough to understand the data, that is not my fault.
Re-read all of the studies, and then let's try again
R
Ross
Guest
Not to mention, increased levels of prolactin DECREASES testosterone levels dramatically.
chazk
New member
- Ross - said:You missed the boat.
You obviously have no scientific background WHATSOEVER.
If you aren't intelligent enough to understand the data, that is not my fault.
Re-read all of the studies, and then let's try again
Do not need to read your studies ross they are done with castrated hamsters,guniepigs and large male rats .
I'll stick with studies that used human test subjects.
Prolactin gets to high hpta shut down .
prolactin gets to low hpta shut down including low Lh and gh output.
Prolactin needs to be in the normal range while on cycle if one wants to still stimulate GH and LH output cuasing androgen uptake.
Try reading the human studies ross....Maybe you prefer the castrated hamster studies? Let me ask you are you a male test rat in a lab ? Are you a castrated hamster? If so then the studies you provided might be good
enough for you.But the rest of us prefer human studiesand will stick with reading those.
You mentioned pituitary tumors? You never mentioned if they were active or non active?
A active pituitary tumor of the prolactin control.Cuases the prolactin levels to get to high cuasing hpta shut down..
A non active blocking pituitary tumor cuases the prolactin to be " blocked of stopped" resulting in hpta shut down along with Lh and Gh output to be dramatically reduced.
Show me one human study ross to back up your claim that next to nothing prolactin levels "trick the body " into not shutting down during a cycle.
So far you have not provided one single study with HUMAN TEST subjects.Ross please provide something besides your male rats,and castrated hamster ramblings.
broc/dos/caber is not needed every cycle .When prolactin is not a issue and surpressing prolactin down below normal be ready to lose LH output along with reduced GH output and androgen uptake.
Your theory looked good in your head ross or on your paper But with human studies done to verify that levels being to low or two high both cuase the same exact shut down and low levels even cuases Lh and Gh out put to be hindered.Suggesting every one lower prolactin levels to subpar levels every cycle when its not needed is just plain and simple giving out bad misiformed advice to the entire community.
This has nothing to do with you ross as a person .Please relize this is for the SAFTY of elite members and their HEALTH is at risk.
I have human studies that support these claims when prolactin is to LOW or to HIGH that hpta shutdown will occur.
So far you have not provided one study that super low levels of prolactin " trick " the hpta into not shutting down.
