Androgens and PRL (Prolactin)

[swifto]

I know this is a somewhat greay area, but is there any evidence confirming andorgens (19-Nors or others) increase PRL (prolactin) in males?

AAS seem to lower T3. Therfore prolactin seems to increase, but apart from that I cannot find anything on it.

Does PgR binding in the hypothalamus increase prolactin levels?

Why do user-s of 19-Nor's experience lactation? I know lactation in males is not solely attributed to prolactin, as hypoongondal males also experience this side effect. I have also read that an out of balance androgen:estrogen ratio can contribute or be a causative factor.

BigCat says no.

Conciliator, Bill Roberts, Dr. Michael Scally, please share your input...

Thank-you.

 

[bigrobbie]

I know this is a somewhat greay area, but is there any evidence confirming andorgens (19-Nors or others) increase PRL (prolactin) in males?

AAS seem to lower T3. Therfore prolactin seems to increase, but apart from that I cannot find anything on it.

Does PgR binding in the hypothalamus increase prolactin levels?

Why do user-s of 19-Nor's experience lactation? I know lactation in males is not solely attributed to prolactin, as hypoongondal males also experience this side effect. I have also read that an out of balance androgen:estrogen ratio can contribute or be a causative factor.

BigCat says no.

Conciliator, Bill Roberts, Dr. Michael Scally, please share your input...

Thank-you.

Yes, T3 is lowered and contributes to Prolactin production, but at the same time if you, as a male, keep your estrogen levels under control Prolactin production and lactation in men

won't happen. But it is hard to find anything spacific on 19-Nor's and prolactin production, I think

this is because it is still being debated. I've read both sides and the more I read, the more I realize I have to learn....Sorry I wasn't much help bro.....Anyone else??

 

[swifto]

Yes, T3 is lowered and contributes to Prolactin production, but at the same time if you, as a male, keep your estrogen levels under control Prolactin production and lactation in men

won't happen. But it is hard to find anything spacific on 19-Nor's and prolactin production, I think

this is because it is still being debated. I've read both sides and the more I read, the more I realize I have to learn....Sorry I wasn't much help bro.....Anyone else??

Not many of the greater minds in our community have come to a conclusion on this. Yet research companies openly sell dopamine agonists to reduce "prolactin gyno". I wonder if it even exists. In the research put forward by BigCat, it doesnt.

But thanks.

 

[Bill Roberts]

Yes, it's been measured on occasion.

One study I read a while back was interesting in that, among other parameters, it measured prolactin levels both for male athletes using a testosterone ester and those using a nandrolone ester each at individual dosage levels, and gave results for each subject rather than simply a combined statistic.

Some of the men using testosterone had large increases in prolactin; many had no increase.

Among those using nandrolone, increase in prolactin seemed more frequent (I didn't run statistics on it and don't recall any conclusion given in the article on it) but there were still many subjects who showed no increase.

Or as another finding in this area, not that it must necessarily be the same for man, but I found at least one veterinary study demonstrating no prolactin increase from trenbolone. I was looking for this specifically because of claims of increasing prolactin.

Many claims in bb'ing regarding prolactin are made without evidence.

However, if an individual finds cabergoline to help him, then very good. It would be nice for the sake of knowledge if he actually had had prolactin tested beforehand, but this seems at best rarely to be done.

But in conclusion, is it a fact that for example Deca must raise prolactin in all users? No.

Is it a fact that both testosterone (for example) and Deca can raise prolactin in some users? Yes.

 

[swifto]

Yes, it's been measured on occasion.

One study I read a while back was interesting in that, among other parameters, it measured prolactin levels both for male athletes using a testosterone ester and those using a nandrolone ester each at individual dosage levels, and gave results for each subject rather than simply a combined statistic.

Some of the men using testosterone had large increases in prolactin; many had no increase.

Among those using nandrolone, increase in prolactin seemed more frequent (I didn't run statistics on it and don't recall any conclusion given in the article on it) but there were still many subjects who showed no increase.

Or as another finding in this area, not that it must necessarily be the same for man, but I found at least one veterinary study demonstrating no prolactin increase from trenbolone. I was looking for this specifically because of claims of increasing prolactin.

Many claims in bb'ing regarding prolactin are made without evidence.

However, if an individual finds cabergoline to help him, then very good. It would be nice for the sake of knowledge if he actually had had prolactin tested beforehand, but this seems at best rarely to be done.

But in conclusion, is it a fact that for example Deca must raise prolactin in all users? No.

Is it a fact that both testosterone (for example) and Deca can raise prolactin in some users? Yes.

Do you have this paper to hand? I'd like to read it.

Would you say its more common for AAS user's to experience raised PRL levels when using exogenous testosterone WITH a 19-Nor?

This agrees with my stance on the subject. That it is very subjective. There is no real reason to always use some sort of PRL control using 19-Nors. But one should keep it on hand.

Do you agree that PRL is not solely responsible for lactation in males? But a contributing factor?

Thank-you.

 

[bigrobbie]

Yes, it's been measured on occasion.

One study I read a while back was interesting in that, among other parameters, it measured prolactin levels both for male athletes using a testosterone ester and those using a nandrolone ester each at individual dosage levels, and gave results for each subject rather than simply a combined statistic.

Some of the men using testosterone had large increases in prolactin; many had no increase.

Among those using nandrolone, increase in prolactin seemed more frequent (I didn't run statistics on it and don't recall any conclusion given in the article on it) but there were still many subjects who showed no increase.

Or as another finding in this area, not that it must necessarily be the same for man, but I found at least one veterinary study demonstrating no prolactin increase from trenbolone. I was looking for this specifically because of claims of increasing prolactin.

Many claims in bb'ing regarding prolactin are made without evidence.

However, if an individual finds cabergoline to help him, then very good. It would be nice for the sake of knowledge if he actually had had prolactin tested beforehand, but this seems at best rarely to be done.

But in conclusion, is it a fact that for example Deca must raise prolactin in all users? No.

Is it a fact that both testosterone (for example) and Deca can raise prolactin in some users? Yes.

Am I wrong in my thought that in order for PRL to become a problem for the male AAS user, that

male must first have elevated estrogen levels...in other words, keep the estrogen in check, and

prolactin shouldn't be a problem. If I'm way off base please correct, thanks!

 

[Michael Scally MD]

Sodi R, Fikri R, Diver M, Ranganath L, Vora J. Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 2005;42(Pt 2):153-9.

Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.


Gill-Sharma MK. Prolactin and male fertility: the long and short feedback regulation. Int J Endocrinol 2009;2009:687259.

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.


Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma J Clin Endocrinol Metab 2002;87(10):4447-51.

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 micro g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 micro g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 micro g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.


Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 1987;64(2):391-4.

Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.

 

[swifto]

Sodi R, Fikri R, Diver M, Ranganath L, Vora J. Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 2005;42(Pt 2):153-9.

Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.


Gill-Sharma MK. Prolactin and male fertility: the long and short feedback regulation. Int J Endocrinol 2009;2009:687259.

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.


Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma J Clin Endocrinol Metab 2002;87(10):4447-51.

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 micro g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 micro g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 micro g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.


Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 1987;64(2):391-4.

Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.

Thank-you.

But doesnt this have limited applicability becuase there not healthy eugondal males?

From what I understand. PRL is regulated by testosterone (long feedback) and also estrogen at the anterior pituitary.

Do you have any information on 19-Nors and PRL? Would they raise PRL moreso, than, for example, a compound that aromotases, such as Testosterone?

Is estrogen that important for PRL synthesis? From what I understand, it seems so as Arimidex (when introduced to to exogenous T) reduced PRL.

 

[bigrobbie]

Thank-you.

But doesnt this have limited applicability becuase there not healthy eugondal males?

From what I understand. PRL is regulated by testosterone (long feedback) and also estrogen at the anterior pituitary.

Do you have any information on 19-Nors and PRL? Would they raise PRL moreso, than, for example, a compound that aromotases, such as Testosterone?

Is estrogen that important for PRL synthesis? From what I understand, it seems so as Arimidex (when introduced to to exogenous T) reduced PRL.

Hard as shit ta get an answer on this one ain't it?! I've seen this debate here at Meso before....

This could get interesting!!! lol

 

[Michael Scally MD]

The answers to your questions are fairly obvious. If the compound aromatizes, interacts with the estradiol receptor, then there will be an effect on prolactin secretion. The same effects would be expected in a "healthy" person taking AAS. The abstracts above address the questions directly. The estradiol produced from testosterone in TRT will "overpower" the negative dopamine agonist effect of cabergoline, therefore the use of an aromatization inhibitor.

An overview of the regulation of prolactin secretion. Prolactin secretion is paced by a light-entrained circadian rhythm, which is modified by environmental input, with the internal milieu and reproductive stimuli affecting the inhibitory or stimulatory elements of the hypothalamic regulatory circuit. The final common pathways of the central stimulatory and inhibitory control of prolactin secretion are the neuroendocrine neurons producing prolactin inhibiting factors (PIF), such as dopamine (DA), somatostatin (SST), and gamma-aminobutyric acid (GABA), or prolactin releasing factors (PRF), such as thyrotropin releasing hormone (TRH), oxytocin (OT), and neurotensin (NT).

PIF and PRF from the neuroendocrine neurons can be released either at the median eminence into the long portal veins or at the neurointermediate lobe, which is connected to the anterior lobe of the pituitary gland by the short portal vessels. Thus lactotrophs are regulated by blood-borne agents of central nervous system or pituitary origin (alpha-melanocyte stimulating hormone) delivered to the anterior lobe by the long or short portal veins. Lactotrophs are also influenced by PRF and PIF released from neighboring cells (paracrine regulation) or from the lactotrophs themselves (autocrine regulation).



Direct effects of neurotransmitters, neuromodulators, and peripheral hormones on the activity of tuberoinfundibular dopaminergic system (TIDA). The inhibitory agents (left) will promote an increase of prolactin secretion as a result of diminishing TIDA activity. On the other hand, the stimulatory neurotransmitters and progesterone (right) will tend to decrease prolactin secretion as a result of increasing output of TIDA neurons.

It should be noted, however, that many of these agents have multiple levels of action, often with opposing biological effect. Therefore, in some cases (*), effects on PRF and/or directly at the lactotrophs will prevail over the influence on TIDA activity.

Key: 5-HT, serotonin; NE, norepinephrine; HA, histamine; EOP, endogenous opioid peptides (endorphin, enkephalin, dynorphin, nociceptin/orphanin); GAL, galanin; SST, somatostatin; CCK8, cholecystokinin-8; GABA, gamma-aminobutyric acid; NO, nitric oxide; ACh, acetylcholine; TRH, thyrotropin releasing hormone; OT, oxytocin; VP, vasopressin; VIP, vasoactive intestinal polypeptide; PACAP, pituitary adenylate cyclase-activating peptide; ANG II, angiotensin II; NT, neurotensin; NPY, neuropeptide Y; CT, calcitonin; BOM, bombesin-like peptides (gastrin-releasing peptide, neuromedin B, neuromedin C); ANP, atrial natriuretic peptides.

But in conclusion, is it a fact that for example Deca must raise prolactin in all users? No.

Is it a fact that both testosterone (for example) and Deca can raise prolactin in some users? Yes.

 

[swifto]

The answers to your questions are fairly obvious. If the compound aromatizes, interacts with the estradiol receptor, then there will be an effect on prolactin secretion. The same effects would be expected in a "healthy" person taking AAS. The abstracts above address the questions directly. The estradiol produced from testosterone in TRT will "overpower" the negative dopamine agonist effect of cabergoline, therefore the use of an aromatization inhibitor.

An overview of the regulation of prolactin secretion. Prolactin secretion is paced by a light-entrained circadian rhythm, which is modified by environmental input, with the internal milieu and reproductive stimuli affecting the inhibitory or stimulatory elements of the hypothalamic regulatory circuit. The final common pathways of the central stimulatory and inhibitory control of prolactin secretion are the neuroendocrine neurons producing prolactin inhibiting factors (PIF), such as dopamine (DA), somatostatin (SST), and gamma-aminobutyric acid (GABA), or prolactin releasing factors (PRF), such as thyrotropin releasing hormone (TRH), oxytocin (OT), and neurotensin (NT).

PIF and PRF from the neuroendocrine neurons can be released either at the median eminence into the long portal veins or at the neurointermediate lobe, which is connected to the anterior lobe of the pituitary gland by the short portal vessels. Thus lactotrophs are regulated by blood-borne agents of central nervous system or pituitary origin (alpha-melanocyte stimulating hormone) delivered to the anterior lobe by the long or short portal veins. Lactotrophs are also influenced by PRF and PIF released from neighboring cells (paracrine regulation) or from the lactotrophs themselves (autocrine regulation).

View attachment 7320

Direct effects of neurotransmitters, neuromodulators, and peripheral hormones on the activity of tuberoinfundibular dopaminergic system (TIDA). The inhibitory agents (left) will promote an increase of prolactin secretion as a result of diminishing TIDA activity. On the other hand, the stimulatory neurotransmitters and progesterone (right) will tend to decrease prolactin secretion as a result of increasing output of TIDA neurons.

It should be noted, however, that many of these agents have multiple levels of action, often with opposing biological effect. Therefore, in some cases (*), effects on PRF and/or directly at the lactotrophs will prevail over the influence on TIDA activity.

Key: 5-HT, serotonin; NE, norepinephrine; HA, histamine; EOP, endogenous opioid peptides (endorphin, enkephalin, dynorphin, nociceptin/orphanin); GAL, galanin; SST, somatostatin; CCK8, cholecystokinin-8; GABA, gamma-aminobutyric acid; NO, nitric oxide; ACh, acetylcholine; TRH, thyrotropin releasing hormone; OT, oxytocin; VP, vasopressin; VIP, vasoactive intestinal polypeptide; PACAP, pituitary adenylate cyclase-activating peptide; ANG II, angiotensin II; NT, neurotensin; NPY, neuropeptide Y; CT, calcitonin; BOM, bombesin-like peptides (gastrin-releasing peptide, neuromedin B, neuromedin C); ANP, atrial natriuretic peptides.

View attachment 7321

Excellent. Thank-you.

 

[RollinsClone]

Dr. Schally, could you help us understand estrogens role in all of this. I know you said compounds can act at the PRF and PIF levels of PRL regulation, so would it be reasonable to assume that estrogen acts on the lactotroph cells themselves (or a pituitary cell controlling the lactotroph) Does estrogen act through it's own receptor or through binding to a related receptor? I realize that these questions may not have been answered yet and that research must still be done to elucidate some of these mechanisms, but just from what you've read/researched could you shed some light?

Thanks and awesome info!

The answers to your questions are fairly obvious. If the compound aromatizes, interacts with the estradiol receptor, then there will be an effect on prolactin secretion. The same effects would be expected in a "healthy" person taking AAS. The abstracts above address the questions directly. The estradiol produced from testosterone in TRT will "overpower" the negative dopamine agonist effect of cabergoline, therefore the use of an aromatization inhibitor.

An overview of the regulation of prolactin secretion. Prolactin secretion is paced by a light-entrained circadian rhythm, which is modified by environmental input, with the internal milieu and reproductive stimuli affecting the inhibitory or stimulatory elements of the hypothalamic regulatory circuit. The final common pathways of the central stimulatory and inhibitory control of prolactin secretion are the neuroendocrine neurons producing prolactin inhibiting factors (PIF), such as dopamine (DA), somatostatin (SST), and gamma-aminobutyric acid (GABA), or prolactin releasing factors (PRF), such as thyrotropin releasing hormone (TRH), oxytocin (OT), and neurotensin (NT).

PIF and PRF from the neuroendocrine neurons can be released either at the median eminence into the long portal veins or at the neurointermediate lobe, which is connected to the anterior lobe of the pituitary gland by the short portal vessels. Thus lactotrophs are regulated by blood-borne agents of central nervous system or pituitary origin (alpha-melanocyte stimulating hormone) delivered to the anterior lobe by the long or short portal veins. Lactotrophs are also influenced by PRF and PIF released from neighboring cells (paracrine regulation) or from the lactotrophs themselves (autocrine regulation).

View attachment 7320

Direct effects of neurotransmitters, neuromodulators, and peripheral hormones on the activity of tuberoinfundibular dopaminergic system (TIDA). The inhibitory agents (left) will promote an increase of prolactin secretion as a result of diminishing TIDA activity. On the other hand, the stimulatory neurotransmitters and progesterone (right) will tend to decrease prolactin secretion as a result of increasing output of TIDA neurons.

It should be noted, however, that many of these agents have multiple levels of action, often with opposing biological effect. Therefore, in some cases (*), effects on PRF and/or directly at the lactotrophs will prevail over the influence on TIDA activity.

Key: 5-HT, serotonin; NE, norepinephrine; HA, histamine; EOP, endogenous opioid peptides (endorphin, enkephalin, dynorphin, nociceptin/orphanin); GAL, galanin; SST, somatostatin; CCK8, cholecystokinin-8; GABA, gamma-aminobutyric acid; NO, nitric oxide; ACh, acetylcholine; TRH, thyrotropin releasing hormone; OT, oxytocin; VP, vasopressin; VIP, vasoactive intestinal polypeptide; PACAP, pituitary adenylate cyclase-activating peptide; ANG II, angiotensin II; NT, neurotensin; NPY, neuropeptide Y; CT, calcitonin; BOM, bombesin-like peptides (gastrin-releasing peptide, neuromedin B, neuromedin C); ANP, atrial natriuretic peptides.

View attachment 7321