[Dynseli]

Green-tea may be counterproductive because of its caffeine effects, other than that it upregulates ER-alpha, and lowers DHT. If green-tea upregulates ER-alpha, that could imply it antagonizes (works against) it. Many hormones that increase sensitivity also decrease growth. Hormones that cause growth also decrease sensitivity, this has potential for cycling another phytohormone that causes growth. Being able to cycle 3 hormone types is better than being able to cycle just 2.

Either caffeine or green tea being an ER-alpha antagonist could explain why green tea is used for herbal reduction.

[Lotus]

Prolactin is a hormone that’s made by your pituitary gland.

High levels of prolactin suppress TSH or Thyroid-Stimulating Hormone. Prolactin is balanced by progesterone and dopamine, so when people have a dopamine deficiency, or progesterone deficiency, their prolactin will increase, and that will decrease the function of the pituitary’s production of thyroid-stimulating hormone.

The imbalance will show up on your labs, perhaps, if you’re lucky, as the TSH is low, but not quite out of the reference range. This is why it’s important to know that there are “optimal” or “functional” levels. .

Prolactin also suppresses luteinizing hormone (LH) in women. Excess prolactin can cause infertility. In men, excess prolactin depresses testosterone so they have low libido. High prolactin can cause tumors that are called prolactinomas.


Prolactin is stimulated by:

stress
low dopamine
low tyrosine
a lack of protein in the diet
oestrogen
contraceptives/HRT
antipsychotics
tranquillisers
gastro-oesophageal reflux drugs
some cancer drugs
some anti-hypertensive drugs
ramelteon (a sleep agent)
any drug which depletes dopamine
Minoxidil (used to promote hair growth in men)
some SSRI and SNRI medications
disease in the liver, kidneys, ovaries and thyroid
prolactinoma (a pituitary tumour)
excess thyrotropin-releasing hormone (TRH), usually in primary hypothyroidism
pregnancy and lactation
some sexual disorders
polycystic ovary syndrome
phytoestrogens

The major source of prolactin are specialised cells called lactotrophs found in the anterior pituitary. Although prolactin is also synthesised and secreted by other tissues such as endothelial, neuronal, and immune cells.

[Lotus]

Excessive estrogen in circumstances of deficient progesterone induces a decrease in receptor sensitivity. One of progesterone's functions is to restore the normal sensitivity of estrogen receptors. When progesterone is restored, estrogen receptor sensitivity is restored also.

________________________________

There are a number of studies showing that estradiol can stimulate prolactin production.

Prolactin synthesis in primary cultures of pituitary cells: Regulation by estradiol
http://www.sciencedirect.com/science/art...0782900843

Evidence That Autoregulation of Prolactin Production Does Not Occur at the Pituitary Level
http://press.endocrine.org/doi/abs/10.12...-110-3-722

Estrogen control of prolactin synthesis in vitro
http://www.pnas.org/content/75/12/5946.short

Prolactin Secretion in vitro
Effects of Gonadal and Adrenal Cortical Steroids.
http://ebm.sagepub.com/content/117/2/579.abstract

Effects of Estradiol and Progesterone on Plasma Gonadotropins, Prolactin, and LHRH in Specific Brain Areas of Ovariectomized Rats
http://www.biolreprod.org/content/24/4/820.short


During pregnancy women produce Estetrol (E4), or 15α-hydroxyestriol, an estrogen steroid hormone, found in detectable levels in maternal serum at around week 20.

Estetrol reaches the maternal circulation through the placenta and was already detected at nine weeks of pregnancy in maternal urine.[6][7] During the second trimester of pregnancy high levels were found in maternal plasma, with steadily rising concentrations of unconjugated E4 to about 1 ng/mL (> 3 nmol/L) towards the end of pregnancy.[8][9] So far the physiological function of E4 is unknown. The possible use of E4 as a marker for fetal well-being has been studied quite extensively. However, due to the large intra- and inter-individual variation of maternal E4 plasma levels during pregnancy this appeared not to be feasible.

Since 2001 E4 has been studied extensively. High oral absorption and bioavailability with a 2–3 hours elimination half-life in the rat has been established.[15] In the human E4 showed a high and dose-proportional oral bioavailability and a long terminal elimination half-life of about 28 hours.[16]

Results from in vitro studies showed that E4 binds highly selective to the estrogen receptors with preference for the ERα form of the receptor unlike ethinyl estradiol (EE) and 17β-estradiol (E2).[17] Also in contrast with EE and especially with E2, E4 does not bind to sex hormone binding globulin (SHBG) and does not stimulate the production of SHBG in vitro.[18]

The properties of E4 have also been investigated in a series of highly predictive, well validated pharmacological in vivo rat models. In these models, E4 exhibited estrogenic effects on the vagina, the uterus (both myometrium and endometrium), body weight, bone mass, bone strength, hot flushes and on ovulation (inhibition).[19][20][21][22] All these effects of E4 were dose-dependent with maximal effects at comparable dose levels. Surprisingly, E4 prevented tumour development in a DMBA mammary tumour model to an extent and at a dose level similar to the anti-estrogen tamoxifen and to ovariectomy.[23] This anti-estrogenic effect of E4 in the presence of E2 has also been observed in in vitro studies using human breast cancer cells [in-house data Pantarhei Bioscience B.V., The Netherlands].

The data indicate that E4 may be suitable for use in several indications e.g. contraception, hormone replacement therapy (both vasomotor symptoms and vulvar vaginal atrophy), breast cancer and osteoporosis. Estetrol is being developed as estrogenic component in the oral contraceptive pill by Estetra (Belgium). Pantarhei Bioscience B.V. (The Netherlands) is developing estetrol for hormone replacement therapy, breast cancer and osteoporosis.

http://wikipedia.org/wiki/Estrogen
____________________________________________________

High Estrogen Levels While Breastfeeding

During pregnancy, circulating levels of the sex hormones estrogen and progesterone rise to prepare your body for lactation. After you give birth, however, levels of these hormones drop as your body increases production of prolactin. As levels of this lactation-inducing hormone increase with decreasing estrogen levels, high estrogen levels after you give birth may make it difficult for you to breastfeed your baby.

Estrogen and Prolactin
In a typical pregnancy, estrogen levels rise to promote the development of milk ducts in your breasts. While high estrogen levels help to prevent you from lactating during your pregnancy, they also trigger the production of prolactin to prepare you for lactation after giving birth. Once prolactin levels reach a certain point, they prevent the ongoing production of estrogen. As such, estrogen levels typically drop toward the end of your pregnancy as prolactin levels rise, allowing you to breastfeed normally after you give birth.

Estrogen Dominance
While they typically drop after you give birth, estrogen levels may remain high despite your body's boost in prolactin production. This may be due to a condition known as estrogen dominance, which involves high levels of estrogen and low levels of progesterone. As these high levels of estrogen mimic those of pregnancy, your body may continue to behave as though pregnant after your body's birth. As such, estrogen dominance may block prolactin's milk-producing abilities, potentially preventing you from lactating after you give birth.

Causes
High estrogen levels following pregnancy may arise from exposure to external sources of estrogen or estrogen-like chemicals. These may include hormone-replacement therapies, petrochemicals and solvents, which may be present in cleaning products, cosmetics, soaps and shampoos. Antibiotics, pesticides and growth hormones present in commercially farmed animal products and produce may also contribute to high estrogen levels, because these products can disrupt natural changes in hormone balance. Other causes may include obesity or excess body fat, high fat intake, liver disease, high alcohol consumption, magnesium and vitamin B6 deficiencies, and stress.

Treatments
Regular exercise may help to lower your estrogen levels by lowering stress and body fat, potentially reducing complications that may arise when trying to breastfeed. Reducing your fat and alcohol intake, eating more foods rich in vitamin B6 and magnesium, and replacing commercially-produced food with organically farmed products may also help to reduce post-delivery estrogen levels. Because these lifestyle changes may not have immediate effects, the use of an anti-estrogen drug, such as the steroid clomiphene, may help to quickly reduce estrogen levels and allow you to breastfeed properly.



http://www.livestrong.com/article/500552...stfeeding/

[Dynseli]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601661/ 'Biological characterization of non-steroidal progestins from botanicals used for women’s health' - "Furthermore, phytoprogestins were able to activate P4 [progesterone] signaling in breast epithelial cells without downregulating PR expression."

[Lotus]

Since the topic of SHBG came up I'd like to share this excellent study on it:




Steroid hormones exert a wide variety of effects on growth, development, and differentiation, including important regulatory and behavioral functions within the reproductive system, central nervous system, and adrenal axis. These hormones act by binding to specific intracellular receptor proteins that function as signal transducers and transcription factors to modulate expression of target genes.1,2 Molecular cloning of the steroid hormone receptor genes in humans has been accomplished over the past 15 years (Table 1). Sequence comparison has revealed that steroid hormone receptors belong to a diverse family of ligand-activated gene regulators that share a highly conserved structure and common mechanisms affecting gene transcription.3 The evolutionary relationship among the steroid and nuclear receptors has been deduced by the high conservation in their DNA-binding domains (DBDs) and in their less-conserved ligand-binding domains (LBDs) and indicates that this large group of proteins arose from a common ancestral molecule.3

Members of the Steroid Hormone and Nuclear Receptor Gene Superfamily in Mammalian Tissues


The Steroid Hormone Receptors
http://www.glowm.com/resources/glowm/cd/...5c004.html

   

[Lotus]

Hello-major breakthrough: (sorry geek humor)

Arrival and Entry of Steroid Hormones Into Target Tissue Cells

Steroid hormones are small, hydrophobic, and lipid-soluble molecules derived from cholesterol. They circulate in blood free or bound (95%) to plasma carrier proteins.56,57,58 Sex hormone-binding globulin (SHBG), also known as testosterone-estradiol-binding globulin (TeBG), and androgen-binding protein (ABP) are encoded by the same gene.59 ABP is produced by the Sertoli cells of the testis, and SHBG is produced by the liver and is present in the circulatory system.58 SHBG binds most gonadal steroids, and corticosteroid-binding globulin (CBG or transcortin) binds glucocorticoids and progesterone with different affinities. When circulating levels of steroid hormones exceed the binding capacity of their respective binding proteins, they can then bind nonspecifically and with low affinity to albumin, from which they can readily dissociate and enter target cells.60 The unbound and loosely albumin-bound steroids are believed to be the most biologically important fractions because the steroid is free to diffuse or be actively transported through the capillary wall and lipid plasma membrane bilayer. Extracellular binding proteins may modulate hormone response by regulating the amount of steroid available to the cell.60 The binding capacity of binding globulins is influenced by endocrine status and other factors.57

SHBG binds to a specific cell membrane receptor called sex hormone-binding globulin receptor (SHBG-R) and activates adenylyl cyclase, increasing intracellular cAMP.58 Binding of SHBG to SHBG-R also transfers SHBG into the cell as a consequence of receptor-mediated endocytosis.61 The interaction of SHBG with SHBG-R is inhibited when steroids are bound to SHBG, suggesting that SHBG is an allosteric protein.61 However, if unliganded SHBG is allowed to bind to its receptor on intact cells and an appropriate steroid hormone then is introduced, adenylate cyclase is activated and intracellular cAMP increases.62 After the steroid hormone is in the cytoplasm, it is not clear whether a transport protein is required for movement of the hydrophobic steroid molecule through the aqueous cytoplasm to the receptor, regardless of whether the receptor is cytoplasmic or nuclear in location. The currently accepted model is that the steroid hormone diffuses freel

[Lotus]

Been looking for this a long time:

REGULATION OF RECEPTOR NUMBERS


The half-life of steroid hormone receptors ranges from 2 to 4 hours for ERα 4 hours for AR, 7 to 10 hours for PR, and 19 hours for GR. The relatively long half-life of the steroid hormone receptors strongly suggests that the receptor proteins are recycled before eventual degradation.

Steroid hormones generally autoregulate their receptor levels. Desensitization or downregulation of receptor numbers, measured by decreased ligand binding capacity, occurs in response to exposure to high levels of ligand and involves the reduction in receptor mRNA levels, decreasing the number of available receptors. The receptor gene may be negatively regulated by the hormonal ligand itself through its receptor protein interacting with specific HREs in the gene. Upregulation or self-priming may occur in an analogous fashion. Steroid hormones can regulate receptor levels for other hormones (e.g. E2 increases PR levels in estrogen-responsive tissues). Progesterone can downregulate its own receptors, as well as ERα and ERβ. This increase or decrease in receptor levels in homologous or heterologous regulation can be caused by alterations in receptor gene transcription or decay rates for receptor mRNA or protein. Binding of the cytosolic GR complex to very long 3'-untranslated regions of its receptor mRNA has been reported to cause premature degradation.

[Lotus]

This Changes Everything

[Dynseli]

REGULATION OF RECEPTOR NUMBERS

The half-life of steroid hormone receptors ranges from 2 to 4 hours for ERα 4 hours for AR, 7 to 10 hours for PR, and 19 hours for GR. The relatively long half-life of the steroid hormone receptors strongly suggests that the receptor proteins are recycled before eventual degradation.

The half life of the receptors, or the hormones on the receptors? If that's a direct quote from a paper, I don't get it. If the half-life of a receptor is that short, how does anyone have enough receptors? Or I misunderstood it, or there's something more...

Steroid hormones generally autoregulate their receptor levels. Desensitization or downregulation of receptor numbers, measured by decreased ligand binding capacity, occurs in response to exposure to high levels of ligand and involves the reduction in receptor mRNA levels, decreasing the number of available receptors. The receptor gene may be negatively regulated by the hormonal ligand itself through its receptor protein interacting with specific HREs in the gene. Upregulation or self-priming may occur in an analogous fashion. Steroid hormones can regulate receptor levels for other hormones (e.g. E2 increases PR levels in estrogen-responsive tissues). Progesterone can downregulate its own receptors, as well as ERα and ERβ. This increase or decrease in receptor levels in homologous or heterologous regulation can be caused by alterations in receptor gene transcription or decay rates for receptor mRNA or protein.

I thought progesterone antagonized yet upregulated ER α and β, even though I found nothing solid on this. Perhaps there's more to understand here.

[Lotus]

This info covers recycling of receptor control

----------------------------
The Recycling and Degradation of G-protein Coupled Receptors

G-protein coupled receptors are not always present on the surface of the plasma membrane, instead these receptors are continually being taken into the cell to either be destroyed or to be recycled. Upon agonist binding to the receptor, the receptor becomes predisposed to internalisation. Internalisation involves the bound receptor being taken into the cell by endocytosis via clathrin coated pits which then bud off from the cell surface to form clathrin coated vesicle. Once in the vesicle the bound receptor is taken to endosomes - internal compartments of the cell - from there the receptors can either be recycled back to the plasma membrane, sequestration, or they can be directed to lysosomes where they will be degraded, downregulation.


G-protein coupled receptors have a constitutive rate of internalisation, that is specific to the particular type of receptor. The binding of agonist serves to increase the rate of endocytosed receptors. Even if the agonist dissociates from the receptor before internalisation can occur the receptor will still undergo endocytosis in the usual way. The amount of agonist that is endocytosed is dependent on the dissociation rate of the agonist from the receptor and the receptors natural constitutive endocytosic rate.

The rate of constitutive endocytosis of receptors depends on the number of surface receptors present. The rate will fall as internalisation reaches steady state. The proportion of receptors inside the cell at steady state is influenced by both the rates of endocytosis and recycling.

The process of sequestration is a dynamic one with the receptors constantly cycling between the plasma membrane and endosomes in the presence of the agonist. The process of downregulation involves the accelerated removal of receptor as well as a decrease in the rate of receptor synthesis

The different extents of recycling and degradation for different G-protein coupled receptors indicate that signals operate in early endosomes to determine the subsequent fate of the endocytosed receptor, with recycling to the plasma membrane being the default pathway. These signals have not yet been identified. It is possible that the activation state of the receptor when it reaches the endosome can determine its fate. Continued activation of the receptor in the endosome it is speculated will target the G-protein coupled receptor towards that of the lysosomal pathway. Therefore the fate of the receptor would depend on agonist affinity.

------------------------------

Functional roles of short sequence motifs in the endocytosis of membrane receptors
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751658/

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Molecular Expressions
http://micro.magnet.fsu.edu/cells/endoso...somes.html
http://micro.magnet.fsu.edu/micro/gallery.html

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Constitutive, agonist-accelerated, recycling and lysosomal degradation of GABA-B receptors in cortical neurons
http://www.sciencedirect.com/science/art...3108002480