# FETAL HEAT PRODUCTION AND TEMPERATURE REGULATION

> **NIH NIH R01** · LOMA LINDA UNIVERSITY · 1994 · $258,999

## Abstract

At birth a newborn lamb responds to cold by inducing shivering and
nonshivering thermogenesis, increasing heat production three- to five-
fold.  If a fetal sheep is cooled in utero, however, the response is
minimal.  Even if additional O2 and catecholamines are provided to
simulate birth conditions, the response remains quiescent.  Thermogenic
responses increase and approach newborn levels only after occlusion of
the umbilical cord.

The means by which cord occlusion facilitates thermogenesis is unknown.
One viable possibility is that an inhibitor, perhaps of placental origin,
suppresses thermogenesis before birth.  Upon its removal thermogenesis
begins under the stimulation of elevated catecholamines.  We have
considered several candidates for the proposed inhibitor and have
designed experiments to test each of them.  The hypotheses are as
follows:

1)   Adenosine of placental origin tonically inhibits lipolysis in
     utero.  Removal of the placenta allows thermogenesis to begin.

2)   A circulating eicosanoid, possibly PGE2, tonically suppresses
     thermogenesis in utero.  Diminishing concentrations after birth
     allow thermogenesis to begin.

3)   Growth hormone tonically suppresses thermogenesis before birth.
     Again, diminishing concentrations allow thermogenesis.

To test these hypotheses a series of studies are proposed using the
chronically-prepared, unanesthetized fetal sheep as an animal model.
Birth will be simulated in utero by cooling the amniotic fluid,
ventilating the fetal lungs with O2, and snaring the umbilical cord.  The
compounds of interest and their antagonists will be given.  Fetal
responses will be assessed by changes in plasma glycerol and free fatty
acid concentration, changes in brown fat temperature, and specific
binding of radiolabeled guanosine diphosphate, GDP (an index of
uncoupling protein activity in brown fat).  Whole-body responses will be
characterized by measurements of O2 consumption and core body
temperature.  An additional line of work will test whether nonshivering
thermogenesis occurs in tissues other than brown fat.  Specific tissues
will be tested using vasoactive agents and blockers of Ca2+ flux.

Our goal is to continue to investigate the signals that activate and
control thermogenic responses in the fetal and newborn sheep.  These
studies are directly relevant to treatment of hypothermia in the newborn
human and, more generally, to the control of metabolism and growth.

## Key facts

- **NIH application ID:** 2197365
- **Project number:** 5R01HD016827-12
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **SAM.gov UEI:** SZAKFNU35ZX5
- **Principal Investigator:** GORDON G POWER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $258,999
- **Award type:** 5
- **Project period:** 1982-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197365

## Citation

> US National Institutes of Health, RePORTER application 2197365, FETAL HEAT PRODUCTION AND TEMPERATURE REGULATION (5R01HD016827-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197365. Licensed CC0.

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