Prolactin is an anterior pituitary hormone which is lactogenic and helps milk production in mammals. The statements below are made regarding the mechanism of action of prolactin.

A. The receptors that bind to prolactin lack lintrinsic tyrosine kinase activity.

B. Upon prolactin binding, the receptors dimerize, and associated kinase is activated.

C. Prolactin binding to receptors leads to activation of its intrinsic kinase activity.

D. STAT plays a role in mediating prolactin action. It dimerizes after its phosphorylation to elicit the response.

E. There is not involvement of STAT in prolactin action mechanisms.

Which one of the following options represents the combination of all correct statements?

Correct option is A

Prolactin is a peptide hormone secreted by the anterior pituitary and is primarily responsible for lactogenesis (milk production) in mammals. Its mechanism of action is mediated via cytokine receptor superfamily, which activates JAK-STAT signaling upon ligand binding.

Let’s analyze each statement:

Statement A: The receptors that bind to prolactin lack intrinsic tyrosine kinase activity.  Correct

• Prolactin receptors are members of the cytokine receptor family.
• These receptors do not possess intrinsic tyrosine kinase activity.
• Instead, they rely on associated kinases, primarily Janus kinases (JAKs), to transmit signals.
  

Statement B: Upon prolactin binding, the receptors dimerize, and associated kinase is activated.  Correct

• Ligand binding (prolactin) leads to receptor dimerization.
• This structural change activates JAK2 (a tyrosine kinase) that is non-covalently associated with the receptor.
• This leads to phosphorylation of the receptor and downstream signaling proteins..

Statement C: Prolactin binding to receptors leads to activation of its intrinsic kinase activity. Incorrect

• As stated in Statement A, prolactin receptors do not have intrinsic kinase activity.
• Therefore, this statement is factually incorrect.

Statement D: STAT plays a role in mediating prolactin action. It dimerizes after its phosphorylation to elicit the response.  Correct

• STAT proteins (especially STAT5) are phosphorylated by JAK2 after prolactin receptor activation.
• Phosphorylated STAT proteins dimerize and translocate into the nucleus to regulate transcription of milk protein genes (e.g., casein).
  

Statement E: There is no involvement of STAT in prolactin action mechanisms.  Incorrect

• This contradicts Statement D and known JAK-STAT pathway biology.
• STATs (mainly STAT5) are crucial mediators of prolactin’s action.
  

Information Booster:

1. Prolactin receptors belong to the cytokine receptor family (not tyrosine kinase receptors).
2. JAK2 is the associated tyrosine kinase that gets activated upon prolactin binding.
3. STAT5 is the primary transcription factor involved in prolactin signaling.
4. STAT5 dimerizes post-phosphorylation and enters the nucleus to activate gene transcription.
5. Milk protein gene expression (e.g., casein genes) is regulated by this pathway.
6. This pathway is a classic example of JAK-STAT signaling in cytokine-mediated responses.
7. Prolactin also affects immune cells and reproductive physiology, beyond lactation.