# REGULATION OF HORMONE SYNTHESIS AND SECRETION

> **NIH NIH R01** · YALE UNIVERSITY · 1994 · $225,659

## Abstract

A large increase in concentrations of cytosolic Ca2 ([Ca2+]c) generally
causes release of prolactin, but there are two conditions in which TRH
causes a marked rise in [Ca2+]c but prolactin release is inhibited:  one is
after pretreatment with dopamine and the other is after frequent pulses of
TRH.  Because TRH generates a large spike of [Ca2+]c in these two cases,
the inhibition of prolactin release must occur at a step subsequent to the
use in [Ca2+]c.  The goal is to understand the mechanisms of inhibition by
determining what processes in the cell are no longer able to respond to
increases in [Ca2+]c.  The specific aims are:  1.  To determine if the
activation of the protein kinase C system by TRH still occurs when
prolactin release is inhibited by dopamine pretreatment or by frequent TRH
pulses.  1a) We will determine what isozymes of protein kinase C are
present in normal lactotrophs and if they are still translocated by TRH
when prolactin release is inhibited.  1b) We will determine if TRH is still
capable of phosphorylating a well-characterized substrate of protein kinase
C when prolactin release is inhibited.  2.  To investigate whether
calmodulin-dependent kinases can be activated by TRH when prolactin release
is inhibited.  2a) We will determine whether elongation factor II, the
substrate for Ca2+/calmodulin kinase III, can still by phosphorylated by
TRH when prolactin release is inhibited.  2b) We will investigate whether
TRH causes changes in the phosphorylation state of Ca2+/calmodulin kinase
II and if the changes still occur when release is inhibited.  In these
first two aims, if we find effects, we will characterize them.  3.  To
isolate and characterize proteins whose phosphorylation is stimulated by
TRH when prolactin release occurs but not when prolactin release is
inhibited.  We will determine what kinases can phosphorylate these proteins
and why phosphorylation is inhibited when prolactin release is inhibited.
This aim will extend knowledge of mechanisms of inhibition beyond the
characterized systems described in the first two aims.  The information
gained from these experiments will increase our understanding of
desensitization that occurs beyond the level of second messengers.

## Key facts

- **NIH application ID:** 2196814
- **Project number:** 5R01HD011487-17
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** PRISCILLA S DANNIES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $225,659
- **Award type:** 5
- **Project period:** 1978-01-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196814

## Citation

> US National Institutes of Health, RePORTER application 2196814, REGULATION OF HORMONE SYNTHESIS AND SECRETION (5R01HD011487-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196814. Licensed CC0.

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