Progesterone, Progesterone Receptors and Prolactin

maillol

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This is an interesting paper I came across from 2019 with new research on progesterone's effects on prolactin. Some highlights:

The participation of ovarian steroids in PRL regulation has been
widely discussed in the literature [3,4,10]. A good and well-defined
example is estradiol (E2), described as the most important stimulator of
prolactin secretion during the reproductive cycle and during pregnancy.
At the hypothalamic level, E2 was shown to decrease the expression
and activity of tyrosine hydroxylase (TH), the key enzyme in dopamine
biosynthesis pathway, decreasing DA release [11–13]. In addition, E2
acts at the pituitary level: i) reducing the inhibitory response of DA on
lactotrophs, ii) increasing the number and size of lactotrophs and iii)
inducing specific gene expression [14–17].

In 1982, an in vivo study by Babu and Vijayan reported a decrease in
hypothalamic TH activity in correlation with elevated PRL levels after
acute administration of P4 to OVX rats [27]. Ten years later, Arbogast &
Voogt et al. corroborated this effect responsible for the elevated levels
of PRL during the late afternoon of proestrus [28,31]. Apparently, in
the absence of E2, P4 negatively modulates TH activity. However, the
same authors reported that in co-treatment with E2, P4 reversed the E2-
induced decrease so that TH mRNA levels in the E2+P4-treated rats
were similar to control levels [29].
Does progesterone need a certain level of E2 to be beneficial? If you look at the study referenced here (27) it says
Single injection of 2 mg P suppressed TH activity in contrast to the elevation in enzyme activity following chronic treatment
So it seems this is only an acute effect. Possibly something to do with the idea that progesterone liberates tissue bound estrogen.

Apparently between 15 and 20% of of prolactinoma patients become resistant to dopamine agonists, the usual treatment. Progesterone has been studied on prolactinomas in a number of mouse studies, four are referenced here, 3 positive and 1 negative (in transgenic mice).

The whole section on receptors is worth reading but something that caught my eye was this
On the other hand, in mice pituitaries, nPRs as well as mPRs are
expressed in lactotrophs, being up-regulated by E2 and down-regulated
by progesterone [54].
I've seen this mentioned before in this study Progesterone and the progesterone receptor - PubMed

I don't know what to make of this. Does taking progesterone downregulate progesterone receptors? Is this a bad thing? Again this is in mice and possibly in vitro so maybe not something to worry about but has anyone noticed any tolerance building on progesterone or withdrawal effects after using for a long time?

Back to prolactin, it seems that progesterone lowers prolactin by both increasing dopamine and inhibiting prolactin secretion. So all good stuff just slightly concerned about the receptor downregulation thing.

it was shown that the specific activation of mPRs in lactotroph
cells leads to a decrease in PRL release. This rapid effect was found to be
mediated by i) a decrease in cAMP levels (due to the activation of a G
inhibitory protein), ii) the phosphorylation of ERK, and iii) an increase
in TGFβ1 activation, a potent inhibitor of lactotroph function [78].
Interestingly, mPRs were also found to be highly expressed in the rat
and mouse hypothalamus [73,74]. Recent data demonstrates that about
90% of the total progesterone receptors in the whole hypothalamus
correspond to mPRs, while relative expression of nPRs represents only
10% of the total [79]. Among all isoforms, mPRα and mPRβ are the
most highly expressed in the hypothalamus. Moreover, mPRα activation
in hypothalamic explants (ex vivo), increases dopamine release
contributing, indirectly, to the P4-inhibitory effect on prolactin secretion
(summarized in Fig. 1) [79].
 

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I think all hormones tend to down regulate their "receptors" so this is nothing to worry about. It's the feedback loop.
 
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This as far as I know is false when it comes to androgens. Testosterone upregulate ar receptors
yes that makes perfect sense. I said THEIR receptors. Of course they upregulate other receptors. It's how the body's feedback loop works to prevent overdosing.
 

Matestube

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This is an interesting paper I came across from 2019 with new research on progesterone's effects on prolactin. Some highlights:




Does progesterone need a certain level of E2 to be beneficial? If you look at the study referenced here (27) it says

So it seems this is only an acute effect. Possibly something to do with the idea that progesterone liberates tissue bound estrogen.

Apparently between 15 and 20% of of prolactinoma patients become resistant to dopamine agonists, the usual treatment. Progesterone has been studied on prolactinomas in a number of mouse studies, four are referenced here, 3 positive and 1 negative (in transgenic mice).

The whole section on receptors is worth reading but something that caught my eye was this

I've seen this mentioned before in this study Progesterone and the progesterone receptor - PubMed

I don't know what to make of this. Does taking progesterone downregulate progesterone receptors? Is this a bad thing? Again this is in mice and possibly in vitro so maybe not something to worry about but has anyone noticed any tolerance building on progesterone or withdrawal effects after using for a long time?

Back to prolactin, it seems that progesterone lowers prolactin by both increasing dopamine and inhibiting prolactin secretion. So all good stuff just slightly concerned about the receptor downregulation thing.

Do you think DHT has the same ability as progesterone to "flush" estrogens or at least to dislocate estrogens from their receptor?
 

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